[Indications and success rate of endotracheal emergency intubation in clinical acute and emergency medicine]. / Indikationen und Erfolgsrate der endotrachealen Notfallintubation in der klinischen Akut- und Notfallmedizin.

BACKGROUND: Securing the airway in the emergency department (ED) is a high-stakes procedure; however, the primary success and complication rate are largely unknown in Germany. The aim of this study was a retrospective analysis of prospectively collected resuscitation room data for endotracheal intubation (ETI) regarding indications, performance and complications. METHOD: Between 1 January 2020 and 30 June 2023 all ETIs conducted in the ED (Kliniken Maria Hilf, Moenchengladbach, Germany) were analyzed following approval by the ethics committee (EK 23-369). Primary intubations performed by the anesthesiology department were excluded. The core medical team of the ED underwent a six-week training program including a two-week anesthesia rotation prior to performing ETI in the ED. There were standard operating procedures (SOP) for both rapid sequence induction (RSI) and airway exchange with a placed laryngeal tube (LT) utilizing video laryngoscopy (C-Mac, Storz), rocuronium for relaxation and primary intubation with an elastic bougie. The primary success rate, overall success rate and intubation-related complications were analyzed. Additionally, the factor of consultant ED staff and residents was evaluated with respect to the primary success rate. RESULTS: During the study period 499 patients were intubated by the core ED team and 28 patients underwent airway exchange from LT to ETI. Primary success could be achieved in 489/499 (98.0%) ETI and in 25/28 (89.3%) LT exchange patients. Surgically achieved securing of the airway was carried out in 5/527 (0.9%) patients in a cannot intubate situation and 11/527 (2.2%) patients suffered cardiac arrest minutes after the ETI. The overall first pass success rate of endotracheal tube placement was 514/527 (97.4%). The comparison of the primary success of consultants (168/175; 96.0%) vs. residents 320/325 (98.5%) yielded no significant differences (p = 0.08). CONCLUSION: In clinical acute and emergency medicine, a standardized approach utilizing video laryngoscopy and a bougie following a structured training concept, can achieve an above-average high primary success rate with simultaneous low severe complications in the high-risk collective of critically ill emergency patients in an intrahospital setting.

Temporary oral anticoagulation after MitraClip - a strategy to lower the incidence of post-procedural stroke?

Background: Incidence of stroke within 30 days after percutaneous mitral valve repair using the MitraClip varies from 0.7% and 2.6% between registries. Standard medical treatment after the MitraClip procedure, in the absence of risk factors requiring antithrombotic therapy such as atrial fibrillation, is dual antiplatelet therapy using aspirin and clopidogrel. ESC/EACTS and ACC/AHA surgical guidelines show a Class IIa indication for temporary antithrombotic therapy after mitral valve repair/bioprosthetic valve replacement within the first three months even in patients with no additional risk factors.Methods: 470 patients were treated with the MitraClip receiving oral anticoagulation (Coumadin: INR 2.0-3.0) instead of dual antiplatelet therapy for at least 30 days after the procedure. The incidence of stroke, as well as major adverse events such as bleeding, were analysed in comparison to large registries and multi-centre studies.Results: Incidence of stroke within 30 days was significantly reduced as compared to comparative cohorts (0.2% vs. Median 1.3% [0.7-2.6%]; p < .05). Cardiovascular risk factors such as age, atrial fibrillation, hypertension, diabetes, STS score and prior stroke did not differ significantly between cohorts (ns). Bleeding complications were not increased due to 30 days oral anticoagulation treatment (4.6% vs. Median 7.4% [3.4-13.6%]; ns).Conclusions: Temporary oral anticoagulation might be a strategy to reduce the incidence of stroke within the first 30 days after the MitraClip procedure. Bleeding events were not significantly altered due to temporary oral anticoagulation.

Identification of patients at higher risk for myocardial injury following elective coronary artery intervention.

OBJECTIVES: To evaluate myocardial injury and infarction (MI) following elective percutaneous coronary intervention (PCI). BACKGROUND: The substantially higher analytical power of high-sensitivity troponin (hsTn) assays allows detection of minor cardiac troponin (cTn) levels, which may be useful in monitoring myocardial injury and guiding therapies. METHODS: Serial hsTnT measurements were conducted in patients undergoing elective PCI and were related to the extent of coronary artery disease (CAD) as reflected by the SYNTAX score risk categories and American College of Cardiology/American Heart Association classification of coronary lesions. Myocardial injury and MI were diagnosed according to the second and third versions of universal MI definition. RESULTS: The study population consisted of 530 patients, who were grouped into low (41.3%), intermediate (35.4%), and high (23.3%) SYNTAX risk categories. The treated coronary lesions were classified into A 7.8%, B1 24.1%, B2 21.1%, C1 24.6%, and C2 22.4%. Postprocedural hsTnT increases correlated significantly with the complexity of treated coronary lesions (p < .05) and CAD magnitude (p < .05). Rates of MI type 4a according to the second and third MI definition criteria were 98 (27.5%) and 15 (4.2%) cases in patients with normal baseline hsTnT values (N = 357, 67.4%), as well as 137 (79.2%) and 27 (15.6%) cases in those with elevated baseline hsTnT values (N = 173, 32.6%), respectively. CONCLUSIONS: After elective PCI, cTn releases correlate significantly with lesion complexity and CAD extent. Use of hsTnT assay enables precise monitoring of PCI-related myocardial injury and may identify patients at higher risk for ischemic events, who may benefit from potent platelet inhibition, which needs to be investigated in randomized trials.

Adenosine stress perfusion cardiac magnetic resonance imaging in patients undergoing intracoronary bone marrow cell transfer after ST-elevation myocardial infarction: the BOOST-2 perfusion substudy.

AIMS: In the placebo-controlled, double-blind BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) 2 trial, intracoronary autologous bone marrow cell (BMC) transfer did not improve recovery of left ventricular ejection fraction (LVEF) at 6 months in patients with ST-elevation myocardial infarction (STEMI) and moderately reduced LVEF. Regional myocardial perfusion as determined by adenosine stress perfusion cardiac magnetic resonance imaging (S-CMR) may be more sensitive than global LVEF in detecting BMC treatment effects. Here, we sought to evaluate (i) the changes of myocardial perfusion in the infarct area over time (ii) the effects of BMC therapy on infarct perfusion, and (iii) the relation of infarct perfusion to LVEF recovery at 6 months. METHODS AND RESULTS: In 51 patients from BOOST-2 (placebo, n = 10; BMC, n = 41), S-CMR was performed 5.1 ± 2.9 days after PCI (before placebo/BMC treatment) and after 6 months. Infarct perfusion improved from baseline to 6 months in the overall patient cohort as reflected by the semi-quantitative parameters, perfusion defect-infarct size ratio (change from 0.54 ± 0.20 to 0.43 ± 0.22; P = 0.006) and perfusion defect-upslope ratio (0.54 ± 0.23 to 0.68 ± 0.22; P < 0.001), irrespective of randomised treatment. Perfusion defect-upslope ratio at baseline correlated with LVEF recovery (r = 0.62; P < 0.001) after 6 months, with a threshold of 0.54 providing the best sensitivity (79%) and specificity (74%) (area under the curve, 0.79; 95% confidence interval, 0.67-0.92). CONCLUSION: Infarct perfusion improves from baseline to 6 months and predicts LVEF recovery in STEMI patients undergoing early PCI. Intracoronary BMC therapy did not enhance infarct perfusion in the BOOST-2 trial.

Procedural advantages of a novel coronary stent design with ultra-thin struts and bioabsorbable abluminal polymer coating in an all-comers registry.

Introduction: The implications of novel drug-eluting stent (DES) design modifications including ultra-thin struts and new concepts of polymer coating for procedural efficacy are still unknown. Aim: To evaluate procedural efficacy and short-term safety of a novel DES design. Material and methods: In this all-comers registry, 407 consecutive patients were enrolled upon undergoing percutaneous coronary interventions (PCI) with the thin-strut bioabsorbable abluminal polymer-coated SYNERGY stent. These patients were then compared with the previous 407 patients undergoing PCI performed by the same interventionalists using currently established second-generation DES (Promus Element plus, Xience prime, Resolute Integrity). Several clinical and procedural data were compared, and the coronary artery complexity was assessed by the American College of Cardiology/American Heart Association classification and SYNTAX Score. Results: The study population consisted of 814 patients. A total of 859 Synergy stents were deployed in 480 target vessels in the Synergy group (n = 407), and 904 stents in 469 vessels in the second-generation DES group (n = 407). Coincidentally, target lesions in the Synergy group (A 2.7%, B1 13.8%, B2 38.6%, C 45.0%) were more complex (p < 0.01) than those in the second-generation DES group (A 4.9%, B1 18.7%, B2 42.3%, C 34.2%). In cases with severe lesions (B2/C), the median contrast agent amount and fluoroscopy time were significantly lower in the Synergy group, indicating improved deliverability (110 ml vs. 150 ml; p < 0.01 and 7.2 min vs. 9.1 min; p = 0.01). Rates of in-hospital major adverse cardiovascular events were comparable between the two groups. Conclusions: In an all-comers, real-world PCI population, novel stent design modifications including ultra-thin struts and abluminal bioabsorbable polymer coating are associated with improved procedural performance.

Haemodynamic effects of percutaneous mitral valve edge-to-edge repair in patients with end-stage heart failure awaiting heart transplantation.

AIMS: Functional mitral regurgitation is complicating end-stage heart failure and potential heart transplantation by increasing pulmonary artery pressures. The aim of the present study was to investigate feasibility and haemodynamic effects of percutaneous mitral valve edge-to-edge repair using the MitraClip™ device in patients with end-stage heart failure awaiting heart transplantation. METHODS AND RESULTS: In this retrospective study, we identified nine patients suffering from end-stage heart failure listed for heart transplantation in whom moderate-severe or severe functional mitral regurgitation was recognized and treated with percutaneous mitral valve edge-to-edge repair. Twenty-two patients listed for heart transplantation and presenting with moderate-severe or severe functional mitral regurgitation treated in the pre-MitraClip™ era served as controls. Patients were analysed at two separate time points: MitraClip™ group: pre-procedure and post-procedure (follow-up: 215 ± 53 days) and control group: study entry with recognition of moderate-severe or severe functional mitral regurgitation (follow-up: 197 ± 47 days). Percutaneous mitral valve edge-to-edge repair with the MitraClip™ was feasible and safe in our high-risk end-stage heart failure population. The intervention resulted in significant reduction of mitral regurgitation (grade 3.0 [0.5] to 1.5 [0.5]; P = 0.009), left atrial diameter (51 mm [16] to 49 mm [4]; follow-up MitraClip™ vs. control group P = 0.0497), pulmonary artery pressures (sPA 50 mmHg [15] to 45 mmHg [10]; P = 0.02; mPA 34 mmHg [8] to 30 mmHg [10]; P = 0.02), and New York Heart Association class (3.5 [1.0] to 3.0 [0.5]; P = 0.01) and improved mixed-venous oxygen saturation (57% [11] to 55% [7]; follow-up MitraClip™ vs. control group P = 0.02). No changes in the control group were observed. CONCLUSIONS: MitraClip™ implantation as 'bridge-to-transplant' strategy in patients with end-stage heart failure and severe functional mitral regurgitation awaiting heart transplantation is feasible and appears to result in favourable haemodynamic effects.

NOAC monotherapy in patients with concomitant indications for oral anticoagulation undergoing transcatheter aortic valve implantation.

AIMS: Antithrombotic therapy after transcatheter aortic valve implantation (TAVI) is highly controversial and guideline recommendations are not evidence based. We assessed efficacy and safety of non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy in patients with concomitant indications for OAC undergoing TAVI. METHODS: Among more than 1300 TAVI patients since 2008, 154 patients were identified who received postinterventional NOAC monotherapy. Outcomes were compared to 172 patients treated with vitamin K antagonist (VKA) monotherapy. Thromboembolic as well as bleeding complications were analysed for 6 months after TAVI. RESULTS: Despite high CHA2DS2-Vasc (4.6 ± 1.2), HEMORR2HAGES (4.7 ± 1.9) and HASBLED (2.7 ± 0.8) scores only three major/life-threatening bleedings and four thromboembolic events occurred after NOAC therapy had been initiated post-TAVI. 12 patients (7.8%) died within 6 months after the procedure. Compared to patients being treated with VKA monotherapy, analysis of a combined end-point of post-procedural death, stroke, embolism and severe bleeding revealed no significant differences (17/154 vs. 14/172; p = 0.45). CONCLUSIONS: The results of this study suggest that NOAC therapy without additional antiplatelet treatment is effective and safe in patients with concomitant indications for OAC undergoing TAVI.

Percutaneous repair of mitral valve regurgitation in patients with severe heart failure: comparison with optimal medical treatment.

BACKGROUND: Occurrence of severe mitral valve (MV) regurgitation (MR) is an independent negative predictor of mortality in patients with severe systolic heart failure (HF). This study examines clinical effects and cardiac reverse remodelling in patients with severe systolic HF receiving percutaneous mitral valve repair (PMVR) using MitraClip in comparison to patients receiving optimal medical therapy only. METHODS: Between 2010 and 2014, 86 patients (Society of Thoracic Surgeons score: 10.5% ± 1.2%) with severe HF (left ventricular [LV] ejection fraction; LVEF: 25% ± 2%; LV endsystolic diameter [LVESD]: 55 ± 3 mm) and severe MR received PMVR using MitraClip. Cardiac reverse remodelling and clinical parameters were compared to HF patients with severe MR (from our HF outpatient clinic; n = 69; LVEF: 26% ± 1.4%; LVESD: 53 ± 2 mm) receiving optimal medical therapy (OMT) only. All patients received stable OMT and were characterised by echocardiography, 6-minwalk-distance test and cardiac biomarkers within a 24 months observation period. RESULTS: PMVR in patients with end-stage HF and severe MR resulted in reduction of MR and significant additional cardiac reverse remodelling (LVEF: 26 ± 1.4 vs. 33% ± 2%, p < .05; LVESD: 53 ± 2 vs. 47 ± 2 mm, p < .05) over the 24 months observation period as compared to pharmacologically-only managed comparators. CONCLUSIONS: Both OMT and PMVR cause cardiac reverse remodelling and relief of symptoms in patients with HF and severe MR. PMVR results in significant additional cardiac reverse remodelling compared to pharmacologically-only managed patients.

Percutaneous repair of severe mitral valve regurgitation secondary to chordae rupture in octogenarians using MitraClip.

OBJECTIVES: The aim of this study was to assess feasibility and clinical effectiveness of the MitraClip device in octogenarians suffering from severe mitral valve regurgitation due to chordae rupture. BACKGROUND: The MitraClip procedure is a suitable technique in high-risk surgical patients to achieve safe and effective percutaneous repair of mitral valve regurgitation. Octogenarians show cumulative risk and social aspects hindering mitral valve surgery. No data exists regarding the use of the MitraClip device in high-risk octogenarians suffering from mitral valve chordae rupture. METHODS: Between October 2009 and March 2017 98 high-risk octogenarians (society of thoracic surgeons score [STS]: 9.7% ± 0.8) with mitral valve prolapse and consecutively chordae rupture were treated with the MitraClip after interdisciplinary discussion. RESULTS: Successful mitral valve repair was achieved in 91% of the octogenarians. Repair of the mitral valve caused immediate and significant reduction of dyspnoea (NYHA class: 3.5 ± 0.4 vs 2.0 ± 0.3; P < 0.001), cardiac reverse remodeling (LVESD: 39 ± 0.8 vs 35 ± 0.8; P < 0.01) and amelioration of cardiac biomarkers (NTproBNP (4884 ± 52 ng/L vs 2473 ± 210 ng/L; P < 0.05,). Effects were stable over the 12 months observation period. None of our patients died intraprocedurally. CONCLUSIONS: Percutaneous repair of chordae rupture is feasible and safe in high-risk octogenarians. The MitraClip should be considered to repair severe mitral valve regurgitation due to mitral valve chordae rupture in high-risk octogenarians after interdisciplinary discussion even facing a challenging anatomy.

Short and long-term results after endovascular management of vascular complications during transfemoral aortic valve implantation.

Background Vascular injury and access site complications in the contemporary setting of transcatheter aortic valve implantation (TAVI) are known to be associated with increased mortality and morbidity. The aim of our study was to analyse the feasibility and safety of percutaneous treatment of such vascular complications using a stent graft. Methods Between January 2010 and April 2013, 36 TAVI patients developed severe access site complications and underwent subsequent interventional treatment with a covered stent. Acute treatment success was confirmed by angiography immediately after the implantation of the stent graft, with clinical long-term patency follow-up being assessed by duplex ultrasound. Results Of the 36 patients evaluated, percutaneous treatment of the acute access site bleeding was successful in 35 patients (97%), with one patient requiring surgical intervention due to insufficient haemostasis after stent graft implantation. A subset of 5 patients underwent successful ipsilateral stent graft implantation, either because crossover sheath placement was not feasible (n = 1), or intentionally with an even sheathless approach in an effort to reduce vessel injury (n = 4). After a mean follow-up of 22 ± 8 months, stent graft patency was confirmed by duplex ultrasound in 13 patients with an additional 5 patients reporting to be free from symptoms and claudication. Thirteen patients died within the first 24 months after the procedure, however, none was due to access vessel complications. Five patients were lost for follow-up. Conclusions Our data confirm that endovascular treatment of access site complications related to TAVI is feasible, safe and efficacious, resulting in long-term vascular patency.

Intracoronary autologous bone marrow cell transfer after myocardial infarction: the BOOST-2 randomised placebo-controlled clinical trial.

AIMS: Intracoronary infusion of autologous nucleated bone marrow cells (BMCs) enhanced the recovery of left ventricular ejection fraction (LVEF) after ST-segment elevation myocardial infarction (STEMI) in the randomised-controlled, open-label BOOST trial. We reassessed the therapeutic potential of nucleated BMCs in the randomised placebo-controlled, double-blind BOOST-2 trial conducted in 10 centres in Germany and Norway. METHODS AND RESULTS: Using a multiple arm design, we investigated the dose-response relationship and explored whether γ-irradiation which eliminates the clonogenic potential of stem and progenitor cells has an impact on BMC efficacy. Between 9 March 2006 and 16 July 2013, 153 patients with large STEMI were randomly assigned to receive a single intracoronary infusion of placebo (control group), high-dose (hi)BMCs, low-dose (lo)BMCs, irradiated hiBMCs, or irradiated loBMCs 8.1 ± 2.6 days after percutaneous coronary intervention (PCI) in addition to guideline-recommended medical treatment. Change in LVEF from baseline (before cell infusion) to 6 months as determined by MRI was the primary endpoint. The trial is registered at Current Controlled Trials (ISRCTN17457407). Baseline LVEF was 45.0 ± 8.5% in the overall population. At 6 months, LVEF had increased by 3.3 percentage points in the control group and 4.3 percentage points in the hiBMC group. The estimated treatment effect was 1.0 percentage points (95% confidence interval, -2.6 to 4.7; P = 0.57). The treatment effect of loBMCs was 0.5 percentage points (-3.0 to 4.1; P = 0.76). Likewise, irradiated BMCs did not have significant treatment effects. BMC transfer was safe and not associated with adverse clinical events. CONCLUSION: The BOOST-2 trial does not support the use of nucleated BMCs in patients with STEMI and moderately reduced LVEF treated according to current standards of early PCI and drug therapy.

Feasibility and safety of vitamin K antagonist monotherapy in atrial fibrillation patients undergoing transcatheter aortic valve implantation.

AIMS: We aimed to assess the efficacy and safety of vitamin K antagonist (VKA) monotherapy in atrial fibrillation (AF) patients undergoing transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: In 735 TAVIs since 2008 we identified 167 patients suffering from concomitant AF who received either VKA monotherapy (n=77), VKA plus single antiplatelet therapy (SAPT, n=41) or a triple anticoagulation regimen (n=49). Thromboembolic as well as bleeding complications were analysed for six months after TAVI. Only one minor bleeding and no thromboembolic events occurred after VKA therapy had been initiated post TAVI. Compared to patients being treated with additional either single or dual antiplatelet therapy, the incidence of major/life-threatening bleeding complications was significantly lower in the VKA mono group (0/77 [VKA mono] vs. 3/41 [VKA+SAPT; p=0.04] vs. 4/49 [triple anticoagulation; p=0.02]). Analysis of a combined endpoint of post-procedural death, stroke, embolism and major bleeding revealed a significant superiority of VKA monotherapy compared to VKA plus SAPT or DAPT, respectively (5/77 vs. 9/41 [p=0.02] vs. 14/49 [p=0.002]). CONCLUSIONS: VKA therapy without additional antiplatelet treatment is effective and safe in AF patients undergoing TAVI.

Initial Single-Center Experience With the Fully Repositionable Transfemoral Lotus Aortic Valve System.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become the standard therapy for patients with severe symptomatic aortic stenosis and unacceptable high risk for surgical aortic valve replacement. Several different devices for TAVR have been introduced so far, each of them with unique features. AIMS: To analyze our first real-world experience with the second- generation, mechanically expanded, fully repositionable transfemoral Lotus TAVR device (Boston Scientific). RESULTS: Between August 2014 and January 2016, a total of 298 patients were scheduled for transfemoral TAVR at our institution. Among them, 145 patients received a CoreValve/CoreValve Evolut R device (Medtronic), 90 patients received a Sapien 3 device (Edwards Lifesciences), and 63 patients were scheduled for Lotus TAVR device implantation based on access vessel size and annulus diameter. Of the 63 subsequent patients scheduled, 62 were successfully implanted. Short-term Valve Academic Research Consortium (VARC)-2 results at 30 days showed a 6.4% all-cause mortality, a 3.2% major stroke rate, a 36.5% new permanent pacemaker rate and 1.6% major vascular complications. Of note was the near absence of significant residual aortic regurgitation in the presence of a favorable hemodynamic profile even in patients with difficult anatomy. CONCLUSION: Our first real-time experience with the fully repositionable Lotus TAVR system mimics the results of early clinical studies like REPRISE II. Further next-generation modifications in combination with gaining experience with this new device will likely reduce the need for new permanent pacemaker implantation and vascular complications in the future.

Improvements of Procedural Results With a New-Generation Self-Expanding Transfemoral Aortic Valve Prosthesis in Comparison to the Old-Generation Device.

OBJECTIVES: In this study, we compare procedural results of our first Evolut R (Medtronic, Minneapolis, MN, USA) implantations with the last CoreValve implantations. Main endpoints include paravalvular regurgitation, major vascular complications, stroke, and pacemaker implantation. BACKGROUND: The evolution of transcatheter aortic valve replacement (TAVR) was possible due to various technical improvements, leading to better periprocedural and long-term outcome. The newly designed Evolut R valve has the potential to further improve TAVR's performance. METHODS: We retrospectively analyzed our first 100 consecutive patients who received the Evolut R valve with the last 100 consecutive patients who received the CoreValve prosthesis between July 2013 and February 2016. Only patients treated with a 26 mm or 29 mm bioprosthesis were included. RESULTS: No significant differences in patient characteristics were noticed. Both angiography and echocardiography after TAVR showed significantly higher rates of "none or trace" regurgitation in the Evolut R group (angiography: 67% Evolut R vs. 29.3% CoreValve; P < 0.001; echocardiography: 68% Evolut R vs. 46.5% CoreValve; P < 0.05). No significant differences were seen in 30-day mortality (7% CoreValve vs. 1% Evolut R), stroke rates (3% CoreValve vs. 2% Evolut R), pacemaker implantation rates (24% CoreValve vs. 23% Evolut R), and major vascular complications (6% CoreValve vs. 1% Evolut R). Implantations were significantly higher with the Evolut R prosthesis. CONCLUSIONS: TAVR with the new Evolut R resulted in significantly lower paravalvular regurgitation. This may be due to redesigned cell geometry and higher precision during implantations, as well as the ability to resheath a malpositioned valve.

Therapeutic hypothermia impacts leukocyte kinetics after cardiac arrest.

BACKGROUND: Patients admitted to the hospital after primarily successful cardiopulmonary resuscitation (CPR) are at a very high risk for neurologic deficits and death. Targeted temperature management (TTM) for mild therapeutic hypothermia has been shown to improve survival compared to standard treatment. Acute cardiovascular events, such as myocardial infarction (MI), are a major cause for cardiac arrest (CA) in patients who undergo CPR. Recent findings have demonstrated the importance and impact of the leukocyte response following acute MI. METHODS: In this retrospective, single center study we enrolled 169 patients with CA due to non-traumatic causes and primarily successful CPR. A total of 111 subjects (66%) underwent TTM aiming for a target temperature of 32-34 °C. RESULTS: Analysis of 30 day follow up showed a significantly improved survival of all patients who received TTM compared to patients without hypothermia (P=0.0001). Furthermore TTM was an independent variable of good neurological outcome after 6 months (P=0.0030). Therapeutic hypothermia was found to be beneficial independent of differences in age and sex between both groups. While a higher rate of pneumonia was observed with TTM, this diagnosis had no additional impact on survival or neurological outcome. The beneficial effect on mortality remained significant in patients with the diagnosis of an acute cardiac event (P=0.0145). Next, we evaluated the kinetics of leukocytes in this group over the course of 7 days after CA. At presentation, patients showed a mean level of 16.5±6.7 of leukocytes per microliter. While this level stayed stable in the group of patients without hypothermia, patients who received TTM showed a significant decline of leukocyte levels resulting in significantly lower numbers of leukocytes on days 3 and 5 after CPR. Interestingly, these differences in leukocyte counts remained beyond the time period of TTM while C-reactive protein (CRP) levels were suppressed only during ongoing cooling, but differences between the groups were diminished after TTM was terminated (from day 3 on, P>0.2). Finally, patients who received TTM and showed a leukocyte count of less than 12.7/µL on day 3 had an improved survival (P=0.0214) and neurological outcome (P=0.0049) compared to patients above that level. CONCLUSIONS: Our data underline the beneficial effects of TTM and demonstrate an impact of hypothermia on leukocyte counts after CA.

Fibroblast growth factor 23 (FGF-23) is an early predictor of mortality in patients with cardiac arrest.

BACKGROUND: Post-cardiac arrest management has seen significant advances with profound improvements in survival and neurologic outcome. However, early prognostication after return of spontaneous circulation remains most challenging. Biomarkers have evolved as helpful tools in identifying patients who are at increased risk of adverse outcome. While fibroblast growth factor 23 (FGF-23) has recently emerged as a promising predictor of mortality in patients with cardiogenic shock, its role in risk stratification in post-resuscitation management remains unresolved. METHODS: This study included 90 patients who had been resuscitated and transferred to the ICU of the University Hospital Heidelberg. Survivors and non-survivors were retrospectively analyzed for known prognostic biomarkers as well as FGF-23 serum levels 24h and 72 h post cardiac arrest (CA). RESULTS: FGF-23 levels were significantly elevated in non-survivors compared to survivors. ROC analysis of FGF-23 levels at 24h and 72 h post CA yielded an AUC of 0.759 and 0.726, respectively, for prediction of overall survival after 6 months. FGF-23 levels remained as significant prognosticators after adjusting for age, renal function, and initial cardiac rhythm. FGF-23 levels did not show significant differences in patient outcome after stratification for cardiac origin of CA or left ventricular dysfunction. Furthermore, FGF-23 levels were moderately predictive of poor neurologic outcome in ROC analysis on day 1 and day 3 post CA with an AUC of 0.738 and 0.687, respectively. CONCLUSION: This study demonstrates elevated FGF-23 serum levels to be potentially helpful in prediction of mortality and poor neurological outcome as early as 24h post cardiac arrest.

Heat-shock-protein 90 protects from downregulation of HIF-1α in calcineurin-induced myocardial hypertrophy.

AIM OF THE STUDY: Capillary/myocyte mismatch is a hallmark of maladaptive myocardial hypertrophy, but the exact mechanisms of this phenomenon remain unknown. We therefore aimed to evaluate the role of calcineurin A in the regulation of hypoxia-inducible factor-1 alpha (HIF-1 alpha) in a calcineurin overexpressing mouse model of myocardial hypertrophy. METHODS AND RESULTS: Mice overexpressing calcineurin A (CnATg) showed persistent upregulation of HIF-1 alpha protein without evidence of a reduction in capillary density despite progressive myocardial hypertrophy. Likewise, overexpression of calcineurin A in isolated cardiomyocytes induced upregulation of HIF-1 alpha protein. In contrast, NFAT-overexpression had no such effect, implying that NFAT-independent mechanisms were responsible for increased HIF-1 alpha levels. In addition, inhibition of HSP90 via the HSP90-inhibitor 17-AAG or siRNA abolished calcineurin A-induced upregulation of HIF-1 alpha. Consequently, upregulation of HIF-1 alpha target genes like VEGF-A, BNIP-3 or PGK-1 was also inhibited by either 17-AAG or siRNA directed against HSP90. Finally, when CnATg mice were treated with 17-AAG, they demonstrated reduced left ventricular function and capillary density. CONCLUSIONS: We describe here for the first time that overexpression of the phosphatase calcineurin A prevents the development of a capillary/myocyte mismatch despite progressive myocardial hypertrophy. This effect was mediated by HSP-90 induced stabilization of HIF-1 alpha. Further work is needed to understand this unexpected cardioprotective effect of calcineurin A.

The extent of aortic annulus calcification is a predictor of postprocedural eccentricity and paravalvular regurgitation: a pre- and postinterventional cardiac computed tomography angiography study.

PURPOSE: To investigate if the extent of aortic valve calcification is associated with postprocedural prosthesis eccentricity and paravalvular regurgitation (PAR) in patients undergoing transcatheter aortic valve implantation (TAVI). METHODS: Cardiac computed tomography angiography (CCTA) was performed before and 3 months after TAVI in 46 patients who received the self-expanding CoreValve and in 22 patients who underwent balloon-expandable Edwards Sapien XT implantation. Aortic annulus calcification was measured with CCTA prior to TAVI and prosthesis eccentricity was assessed with post-TAVI CCTA. Standard echocardiography was also performed in all patients at 3-month follow-up exam. RESULTS: Annulus eccentricity was reduced during TAVI using both implantation systems (from 0.23 ± 0.06 to 0.18 ± 0.07 using CoreValve and from 0.20 ± 0.07 to 0.05 ± 0.03 using Edwards Sapien XT; P<.001 for both). With Edwards Sapien XT, eccentricity reduction at the level of the aortic annulus was significantly higher compared with CoreValve (P<.001). Annulus eccentricity after CoreValve use was significantly related to absolute valve calcification and to valve calcification indexed to body surface area (BSA) (r = 0.48 and 0.50, respectively; P<.001 for both). Furthermore, a significant association was observed between aortic valve calcification and PAR (P<.01 by ANOVA) in patients who received CoreValve. Using ROC analysis, a cut-off value over 913 mm² aortic valve calcification predicted the occurrence of moderate or severe PAR with a sensitivity of 92% and a specificity of 63% (area under the curve = 0.75). Furthermore, multivariable analysis showed that aortic valve calcification was a robust predictor of postprocedural eccentricity and PAR, independent of the aortic annulus size and native valve eccentricity and of CoreValve prosthesis size (adjusted r = 0.46 and 0.50, respectively; P<.01 for both). Such associations were not present with the Edwards Sapien XT system. CONCLUSION: The extent of native aortic annulus calcification is predictive for postprocedural prosthesis eccentricity and PAR, which is an important marker for long-term mortality in patients undergoing TAVI. This observation applies for the CoreValve, but not for the Edwards Sapien XT valve.

First experience with the new generation Edwards Sapien 3 aortic bioprosthesis: procedural results and short term outcome.

BACKGROUND: TAVR has become an established treatment for severe symptomatic aortic stenosis in patients with high surgical risk. The latest generation of the balloon-expandable Edwards Sapien device, the Sapien 3, together with its new transfemoral Commander delivery system has been designed to reduce paravalvular regurgitation and vascular access site complications. OBJECTIVES: To evaluate procedural results and short term outcome with the third generation Sapien 3 device. METHODS: We retrospectively evaluated 125 consecutive TAVR patients and analyzed the first 51 patients in whom we implanted the new Sapien 3 device via transfemoral access. RESULTS: In patients implanted with the Sapien 3 device significant residual paravalvular regurgitation after TAVR was virtually absent with the vast majority having none or trace postinterventional aortic regurgitation on angiography or echocardiography (92.2% and 80.4% respectively). None of the patients had more than mild paravalvular regurgitation. Major vascular access site complications or major bleeding according to the VARC II criteria were not observed in our cohort, minor vascular complications and minor bleeding occurred in 7.8% and 5.9% respectively. If vascular complications occurred, they were related to closure device failure. Thirty day outcome showed a 1.9% major stroke rate and 3.9% death rate. However, we observed a 25.5% permanent pacemaker rate in our Sapien 3 cohort. CONCLUSIONS: Implantation of the new third generation Sapien 3 device resulted in excellent procedural and short term outcome. Significant paravalvular regurgitation was virtually absent. However, the increased rate of postinterventional pacemaker implantations needs to be analyzed in a larger cohort of patients.

Feasibility and clinical benefit of a suture-mediated closure device for femoral vein access after percutaneous edge-to-edge mitral valve repair.

AIMS: We assessed feasibility, efficacy and safety of a suture-mediated closure device, Perclose Proglide (Abbott Vascular Devices, Santa Clara, CA, USA), for closure of the femoral vein access after percutaneous MitraClip (Abbott Vascular Devices) implantation. METHODS AND RESULTS: Venous access of 80 consecutive patients undergoing percutaneous mitral valve repair using the MitraClip device was managed either by manual compression, "figure eight" suture and compression bandage for 12 hours, or by applying the Proglide device for haemostasis after the procedure (40 patients each group). Patients with Proglide closure showed complete immediate haemostasis in 92.5% (37/40) and were immobilised with a compression bandage for only four hours. In the Proglide group, one arteriovenous fistula was observed and had to be treated by vascular surgery. The overall duration of stay on an intensive care unit was significantly reduced in the Proglide group (59.4±48.9 hours vs. 84.6±59.5 hours, p<0.005). CONCLUSIONS: Using a suture-mediated closure device for the femoral vein after percutaneous MitraClip implantation is feasible and safe. This allows earlier patient mobilisation and may reduce post-interventional duration of stay on an intensive care unit.