Search

Approximately one fifth of patients diagnosed with atrial fibrillation (AF) undergo a percutaneous coronary intervention (PCI). Current guidelines recommend different combinations and durations of triple or dual antithrombotic therapy for these patients but data on the implementation of these recommendations in clinical routine are scarce. ENCOURAGE-AF is a prospective, non-interventional, non-comparative, multicentre study. Approximately 720 patients will be consecutively enrolled from 70 participating sites across Germany. Patients with non-valvular AF treated with edoxaban, who have undergone successful PCI, have no planned elective cardiac intervention during the study period, have capability, availability, and willingness for follow-up by telephone interview during the study, are aged ≥ 18 years with life expectancy ≥ 1 year, and provide written informed consent, will be included. Eligible patients will be enrolled between 4- and 72-h after completing a successful PCI. Duration of exposure to and dosing regimens of edoxaban, antiplatelet agents and other concomitant medications of interest will be monitored in line with the clinical practice. Physician- and patient-reported clinical events, adverse drug reactions, patient quality of life (EQ-5D-5L) and health resource utilisation (HRU) parameters will be evaluated at 30 days and 1-year post-PCI. The ENCOURAGE-AF non-interventional study will provide insights into the patterns of edoxaban usage in combination with antiplatelet treatment and other concomitant medications in AF patients with a successful PCI over a 1-year time period during routine clinical practice in Germany. The effectiveness and safety of edoxaban in this patient population, as well as patients' quality of life and HRU will be evaluated. Trial registration: Clinicaltrial.gov NCT04519944, registered on 20 August 2020. [ABSTRACT FROM AUTHOR]

Aims Although the share of women in cardiology in Germany is growing steadily, this does not translate into leadership positions. Medical societies play a crucial role in shaping the national and international medical and scientific environment. The German Cardiac Society (DGK) aims to serve the public discourse on gender-equity by systematic analysis of data on gender representation within the society and in Germany. Methods and results We present gender disaggregated data collection of members, official organs, working groups, scientific meetings, as well as awards of the DGK based on anonymized exports from the DGK office as well as on data gathered from the DGK web page. From 2000 to 2020, the overall number of DGK members as well as the share of women increased (12.5% to 25.3%). In 2021, the share of women ranged from 40% to 50% in earlier career stages but was substantially lower at senior levels (23.9% of consulting/attending physicians, 7.1% of physicians-in-chief, 3.4% of directors). The share of women serving in DGK working groups had gained overall proportionality, but nuclei and speaker positions were largely held by men. Boards and project groups were predominantly represented by men as well. At the DGK-led scientific meetings, women contributed more often in junior relative to (invited) senior roles. Conclusion Increasing numbers of women in cardiology and in the DGK over the past 20 years did not translate into the respective increase in representation of women in leadership positions. There is an urgent need to identify and, more importantly, to overcome barriers towards gender equity. Transparent presentation of society-related data is the first step for future targeted actions in this regard. [ABSTRACT FROM AUTHOR]

Background: Appropriate and timely anticoagulant therapy with vitamin K antagonists (VKAs) or non-vitamin K oral antagonists (NOACs) is essential for stroke prevention in non-valvular atrial fibrillation (NVAF). Comparative data regarding effectiveness and safety for edoxaban vs phenprocoumon, the predominant VKA in Germany, are scarce. Objectives: The study evaluates effectiveness and safety of edoxaban vs phenprocoumon in NVAF patients in a German real-world setting. Methods: German statutory health insurance claims data of the Institute for Applied Health Research Berlin (InGef) Research Database from 2014 until 2019 were analyzed. In NVAF patients, new users of edoxaban and phenprocoumon were compared to assess effectiveness (stroke/systemic embolism (SE)) and safety (bleeding) during therapy. Hazard ratios (HR) were estimated through multiple outcome-specific cox proportional hazard models adjusting for baseline characteristics. Outcomes of geriatric patients were analyzed in subgroup analyses. Results: Between 2015 and 2018, 7,975 and 13,319 NVAF patients newly initiated treatment with edoxaban or phenprocoumon. After adjusting for baseline confounders, the risk of stroke/SE (HR: 0.85, 95% CI: 0.70–1.02) was numerically but not significantly lower, while the risk of major bleeding (HR: 0.69, 95% CI: 0.58–0.81) was significantly lower for edoxaban. In the geriatric subgroups, homogenous results compared to the main analysis were obtained. Conclusion: The results of this real-world analysis indicated better effectiveness and safety outcomes in patients with NVAF initiating edoxaban treatment compared to phenprocoumon. The findings confirm that the beneficial effects observed in the pivotal ENGAGE AF-TMI 48 trial can also be achieved in real-world use of edoxaban. [ABSTRACT FROM AUTHOR]

Aims: The number of transcatheter mitral valve repair (TMVr) procedures has increased substantially during the last years. A better understanding of the relationship between hospital volume of transcatheter transvenous mitral valve repairs using MitraClip® and patient outcomes may provide information for future policy decisions to improve patient management. Methods and results: We analysed patient characteristics and in‐hospital outcomes for all TMVr procedures using MitraClip® performed in Germany from 2011 to 2017. Hospitals were stratified according to centre volumes and patients were compared for baseline characteristics and adverse in‐hospital events. Overall, 24 709 inpatients were treated during the observational period. Patients treated in centres with a volume of ≤10 procedures annually developed more often pulmonary embolism (odds ratio 2.22, 95% confidence interval 1.19–4.13; P = 0.012) compared to those treated in centres with a volume of >10 procedures annually, whereas no association of centre volume (≤10 or >10) was found with in‐hospital mortality (P = 0.728). Although patients treated in centres with an annual volume >25 TMVr procedures had higher numbers of comorbidities compared to those treated in centres with an annual volume of ≤25 TMVr procedures, in‐hospital mortality did not differ (3.6% vs. 3.5%, P = 0.485). Similarly, when centre volumes were stratified for ≤50 vs. >50 procedural volumes, no association with in‐hospital mortality was recorded (P = 0.792). A lower rate of mitral valve surgery after MitraClip® was observed over time, particularly in high‐volume centres. Conclusion: Annual numbers of MitraClip® implantations increased from 2011 to 2017 in Germany, whereas in‐hospital mortality remained stable. Although patients treated in high‐volume centres had a more unfavourable risk profile, in‐hospital mortality was comparable to that of low‐volume centres. [ABSTRACT FROM AUTHOR]

Objective: In patients with pulmonary arterial hypertension (PAH), supportive therapies may be beneficial in addition to targeted medical treatment. Here, we evaluated the effectiveness and safety of oscillatory whole-body vibration (WBV) in patients on stable PAH therapy.Methods: Twenty-two patients with PAH (mean PAP≥25 mm Hg and pulmonary arterial wedge pressure (PAWP)≤15 mm Hg) who were in world health organization (WHO)-Functional Class II or III and on stable PAH therapy for≥3 months, were randomised to receive WBV (16 sessions of 1-hour duration within 4 weeks) or to a control group, that subsequently received WBV. Follow-up measures included the 6-min walking distance (6MWD), cardiopulmonary exercise testing (CPET), echocardiography, muscle-power, and health-related quality of life (HRQoL; SF-36 and LPH questionnaires).Results: When compared to the control group, patients receiving WBV exhibited a significant improvement in the primary endpoint, the 6MWD (+35.4±10.9 vs -4.4±7.6 m), resulting in a net benefit of 39.7±7.8 m (p=0.004). WBV was also associated with substantial improvements in CPET variables, muscle power, and HRQoL. The combined analysis of all patients (n=22) indicated significant net improvements versus baseline in the 6MWD (+38.6 m), peakVO2 (+65.7 mL/min), anaerobic threshold (+40.9 mL VO2/min), muscle power (+4.4%), and HRQoL (SF-36 +9.7, LPH -11.5 points) (all p<0.05). WBV was well tolerated in all patients, and no procedure-related severe adverse events (SAEs) occurred.Conclusions: WBV substantially improves exercise capacity, physical performance, and HRQoL in patients with PAH who are on stable targeted therapy. This methodology may be utilised in structured training programmes, and may be feasible for continuous long-term physical exercise in these patients.Trial Registration Number: NCT01763112; Results. [ABSTRACT FROM AUTHOR]

Aims A substantial percentage of patients with mitral regurgitation (MR) in need of mitral valve repair are currently considered not suitable for conventional surgery. In Germany, the largest cohort of patients studied to date has been treated using a percutaneous, catheter-based approach. We report the acute outcomes of patients enrolled in the investigator-initiated German transcatheter mitral valve interventions (TRAMI) registry. Methods and results Between January 2009 and August 2011, 486 patients [median age 75 (interquartile range 70–80) years; 200 women (41%)] were enrolled in the registry (309 retrospectively and 177 prospectively), with 481 patients (99%) having undergone percutaneous edge-to-edge therapy for MR using the MitraClip. At baseline, 93% of patients were in New York Heart Association (NYHA) functional class III or IV and 71% of patients had a left ventricular ejection fraction (LVEF) ≤50%. Two-thirds of patients presented with functional MR. Procedural success was achieved in 94% of patients, with grade III present in 93% of patients at baseline yet only 6% post-intervention. Retrospective patients were followed for a median of 183 days, prospective patients for a median of 44 days. The periprocedural complication rate was low, with only minor bleedings as the most significant event. In-hospital and post-discharge mortality was 2.5% and 12.5%, respectively. Conclusions Data from the German TRAMI registry suggest that MitraClip therapy is a viable treatment option in daily clinical routine for high surgical risk patients with significant MR. [ABSTRACT FROM AUTHOR]

Abstract Background MitraClip therapy is increasingly used in patients deemed inoperable to treat severe mitral regurgitation (MR), but long-tern data is scarce. Aims The multicentre, industry-independent German Transcatheter Mitral Valve Interventions (TRAMI) registry comprises the largest prospectively enrolled cohort of patients treated by MitraClip therapy. The current analysis is focusing on long-term mortality rates, cardiac rehospitalization and reintervention. Methods and results Long-term follow-up (median time 1037 days) in the TRAMI registry was available for 722 patients treated at 20 German centres. Improvements in New York Heart Association (NYHA) functional class (I/II long-term: 65% vs. 1-year follow-up: 63.3%) and self-rated health-status (EuroQuol visual analogue scale [EQ VAS] long-term: 60 [50–70] vs. 1-year follow-up: 60 [50; 70]) were pertained over time. Estimated mortality rates by Kaplan-Meier method were 19.7% for 1-year, 31.9% for 2-year and 53.1% for 4-year follow-up without differences found for MR aetiology. Multivariable Cox-regression analysis identified previous aortic valve implantation (hazard ratio [HR] = 2.21; p < 0.0001), NYHA class IV (HR = 1.78; p < 0.001), prior cardiac decompensation (HR = 1.63; p < 0.001), creatinine > 1.5 mg/dl (HR = 1.63; p < 0.0001) and left ventricular ejection fraction < 30% (HR = 1.60; p < 0.001) as most predictive for long-term mortality. Conclusions Long-term outcome in the TRAMI registry confirmed lasting clinical improvements and low intervention rates. Long-term mortality was strongly influenced by cardiac and non-cardiac co-morbidities and was found comparable for both MR aetiologies. Highlights • Long-term outcome was analyzed in the German Transcatheter Mitral Valve Interventions (TRAMI) registry comprising 799 patients treated at 20 centers in Germany. • This study demonstrated relevant clinical improvements and low reintervention rates, yet mortality rates exceeding 50% at 4-year follow-up. • To further understand the prognostic potential of MitraClip therapy, reliable evidence of the ongoing RCTs in FMR patients is urgently needed. [ABSTRACT FROM AUTHOR]

Objective: To assess temporal trends of patient baseline characteristics, risk profile and outcome of transcatheter aortic valve implantation (TAVI) between 2013 and 2020., Background: Guideline recommendations and increasing confidence in TAVI therapy may have changed the selection of TAVI patients., Methods: Baseline risk profile and VARC-2 outcome of 15,344 patients undergoing TAVI at 5 high volume centers in Germany over the time period 2013-2020 was analyzed., Results: Over the 8 years, annual TAVI volumes more than doubled from 1071 in 2013 to 2996 in 2020. The baseline surgical risk estimated by the Society of Thoracic Surgeons (STS) score declined from 7.2 ± 6.2% to 4.6 ± 3.7% (P < 0.001) as a consequence of lower comorbidity burden, whereas mean age remained unchanged (2013 81.0 ± 6.1; 2020 80.8 ± 6.4; P = 0.976) with patients ≥ 80 years accounting for about two-third of the treated cohort. Periprocedural complications including bleeding (2013 24.5%; 2020 12.1%; P < 0.001), vascular complications (2013 20.7%; 2020 11.7%; P < 0.001) and new permanent pacemaker implantation (2013 20.1%; 2020 13.8%, P < 0.001) decreased significantly. Similarly, the 30-day mortality decreased from 5.4% to 2.1% (P < 0.001), but remained high in high-risk patients (STS > 8% 2013 7.5%; 2020 6.9%; P = 0.778)., Conclusion: From 2013 to 2020, mortality and burden of complications following TAVI procedure significantly decreased in a large multicenter registry from Germany. Proportion of elderly patients remained stable, while the surgical risk profile decreased., (© 2021. The Author(s).)

Objectives: The aim of this study was to examine predictors and impact of postoperative delirium (POD) on outcome after percutaneous repair of mitral and tricuspid valves., Background: POD is common in elderly patients and contributes to increased health care costs and worse outcome. Predictors of POD in percutaneous mitral or tricuspid valve procedures are unclear., Methods: In a prospective single-center study, patients were screened for POD using the Confusion Assessment Method on the first and second postprocedural days, and up until 7 days in patients with clinical suspicion of delirium. Associations of POD with baseline characteristics, periprocedural outcome and mid-term mortality were examined., Results: One hundred and seventy-seven patients were included (median age 78 years [72-82], 41.8% female) and median (IQR) follow-up was 489 (293-704) days. Patients developing POD (n = 16, 9%) did not differ in baseline and procedural characteristics but more often received postinterventional blood transfusions (37.5% vs. 9.9%, p value = 0.007) and suffered from infections (43.8% vs. 9.9%, p value = 0.001). Patients with POD showed worse survival (HR: 2.71 [1.27-5.78]; p = 0.01), with an estimated 1-year survival of 46 ± 13% compared to 80 ± 3% in patients without POD (log-rank p value 0.007). In multivariate Cox regression, POD remained a significant predictor of mid-term mortality (HR 4.75 [1.97-11.5]; p = 0.001)., Conclusion: After percutaneous mitral or tricuspid valve repair, POD was independently associated with worse mid-term survival. Procedure- rather than patient-associated characteristics such as blood transfusions and infections emerged as important risk factors for development of POD. Considering the substantial prognostic impact of POD, further studies on its prevention are warranted to improve patient outcome., (© 2021. The Author(s).)

Background: Reliable risk scores in patients undergoing transcatheter edge-to-edge mitral valve repair (TMVR) are lacking. Heart failure is common in these patients, and risk scores derived from heart failure populations might help stratify TMVR patients., Methods: Consecutive patients from three Heart Centers undergoing TMVR were enrolled to investigate the association of the "Get with the Guidelines Heart Failure Risk Score" (comprising the variables systolic blood pressure, urea nitrogen, blood sodium, age, heart rate, race, history of chronic obstructive lung disease) with all-cause mortality., Results: Among 815 patients with available data 177 patients died during a median follow-up time of 365 days. Estimated 1-year mortality by quartiles of the score (0-37; 38-42, 43-46 and more than 46 points) was 6%, 10%, 23% and 30%, respectively (p < 0.001), with good concordance between observed and predicted mortality rates (goodness of fit test p = 0.46). Every increase of one score point was associated with a 9% increase in the hazard of mortality (95% CI 1.06-1.11%, p < 0.001). The score was associated with long-term mortality independently of left ventricular ejection fraction, NYHA class and NTproBNP, and was equally predictive in primary and secondary mitral regurgitation., Conclusion: The "Get with the Guidelines Heart Failure Risk Score" showed a strong association with mortality in patients undergoing TMVR with additive information beyond traditional risk factors. Given the routinely available variables included in this score, application is easy and broadly possible., (© 2021. The Author(s).)

Background: Hepatorenal dysfunction is a strong prognostic predictor in patients with heart failure. However, the prognostic impact of the hepatorenal dysfunction in patients undergoing transcatheter mitral valve repair (TMVR) has not been well studied., Methods: In consecutive patients who underwent edge-to-edge TMVR at three German centers, the model for end-stage liver disease excluding international normalized ratio (MELD-XI) score was calculated as 5.11 × ln [serum total bilirubin (mg/dl)] + 11.76 × ln [serum creatinine (mg/dl)] + 9.44. Patients were stratified into high (> 11) or low (≤ 11) MELD-XI score of which an incidence of the composite outcome, consisting of all-cause mortality and heart failure hospitalization, within 2 years after TMVR was assessed., Results: Of the 881 patients, the mean MELD-XI score was 11.0 ± 5.9, and 415 patients (47.1%) had high MELD-XI score. The MELD-XI score was correlated with male, effective regurgitant orifice area, and tricuspid regurgitation severity and inversely related to left ventricular ejection fraction. Patients with high MELD-XI score had a higher incidence of the composite outcome than those with low MELD-XI score (47.7% vs. 29.8%; p < 0.0001), and in multivariable analysis, the high MELD-XI score was an independent predictor of the composite outcome [adjusted hazard ratio (HR) 1.34; 95% confidence interval (CI) 1.02-1.77; p = 0.04). Additionally, the MELD-XI score as a continuous variable was also an independent predictor (adjusted HR 1.02; 95% CI 1.00-1.05; p = 0.048)., Conclusions: The MELD-XI score was associated with clinical outcomes within 2 years after TMVR and can be a useful risk-stratification tool in patients undergoing TMVR., (© 2021. The Author(s).)

Background:  Rapid deployment aortic valve replacement (RDAVR) and transcatheter aortic valve implantation (TAVI) have emerged as increasingly used alternatives to conventional aortic valve replacement to treat patients at higher surgical risk. Therefore, in this single-center study, we retrospectively compared clinical outcomes and hemodynamic performance of two self-expanding biological prostheses, the sutureless and rapid deployment valve (RDV) Perceval-S (PER) and the transcatheter heart valve (THV) ACURATE neo /TF (NEO) in a 1:1 propensity-score-matching (PSM) patient cohort., Methods:  A total of 332 consecutive patients with symptomatic aortic valve stenosis underwent either singular RDAVR with PER (119) or TAVI with NEO (213) at our institutions between 2012 and 2017. To compare the unequal patient groups, a 1:1 PSM for preoperative data and comorbidities was conducted. Afterward, 59 patient pairs were compared with regard to relevant hemodynamic parameter, relevant paravalvular leak (PVL), permanent postoperative pacemaker (PPM) implantation rate, and clinical postoperative outcomes., Results:  Postoperative clinical short-term outcomes presented with slightly higher rates for 30-day all-cause mortality (PER = 5.1% vs. NEO = 1.7%, p  = 0.619) and major adverse cardiocerebral event in PER due to cerebrovascular events (transient ischemic attack [TIA]-PER = 3.4% vs. TIA-NEO = 1.7%, p  = 0.496 and Stroke-PER = 1.7% vs. Stroke-NEO = 0.0%, p  = 1). Moreover, we show comparable PPM rates (PER = 10.2% vs. NEO = 8.5%, p  = 0.752). However, higher numbers of PVL (mild-PER = 0.0% vs. NEO = 55.9%, p  = 0.001; moderate or higher-PER = 0.0% vs. NEO = 6.8%, p  = 0.119) after TAVI with NEO were observed., Conclusion:  Both self-expanding bioprostheses, the RDV-PER and THV-NEO provide a feasible option in elderly and patients with elevated perioperative risk. However, the discussed PER collective showed more postoperative short-term complications with regard to 30-day all-cause mortality and cerebrovascular events, whereas the NEO showed higher rates of PVL., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Low-flow low-gradient (LF-LG) aortic stenosis (AS) is associated with high mortality, even after transcatheter aortic valve replacement (TAVR). Further knowledge of risk indicators is needed and a clinical risk score would be desirable for optimizing patient selection and therapeutic strategy., Methods: The study cohort comprised of 219 consecutive LF-LG AS patients undergoing TAVR from 2008 to 2018 in two high-volume German centers. Predictive factors for one-year all-cause mortality were defined according to a Cox proportional hazard model., Results: At one-year follow-up after TAVR, 28% of patients had died. A multivariate model revealed six independent predictors of one-year mortality: history of myocardial infarction (HR 2.05, 95%CI 1.13-3.72), eGFR < 30 ml/min/1.73m 2 (HR 2.75, 95%CI 1.48-5.11), tricuspid regurgitation moderate or more (HR 2.06, 95%CI 1.14-3.72), stroke volume index < 25 mL/m 2 (HR 2.03, 95%CI 1.14-3.62), self-expandable device (HR 2.72, 95%CI 1.17-6.27), and non-transfemoral approach (HR 3.42, 95%CI 1.28-9.14). The Rhineland Risk Score (RRS) consisting of these variables (c statistic 0.75, 95%CI 0.68-0.82, p < 0.001) was superior to the EuroSCORE II (c statistic 0.63) and STS-PROM score (c statistic 0.69) at predicting one-year mortality. Patients with a RRS ≥ 8 had a prohibitive risk of one-year mortality of 67.6% (95%CI 52.0-82.4%)., Conclusion: In patients with LF-LG AS, history of myocardial infarction, renal dysfunction, tricuspid regurgitation, a low stroke volume index, self-expandable device, and non-femoral approach were associated with increased 1-year mortality after TAVR. The RRS might serve as a helpful tool for risk prediction and patient selection for TAVR in patients with LF-LG AS.

Background: Surgical risk prediction models are routinely used to guide decision-making for transcatheter aortic valve replacement (TAVR). New and updated TAVR-specific models have been developed to improve risk stratification; however, the best option remains unknown., Objective: To perform a comparative validation study of six risk models for the prediction of 30-day mortality in TAVR METHODS AND RESULTS: A total of 2946 patients undergoing transfemoral (TF, n = 2625) or transapical (TA, n = 321) TAVR from 2008 to 2018 from the German Rhine Transregio Aortic Diseases cohort were included. Six surgical and TAVR-specific risk scoring models (LogES I, ES II, STS PROM, FRANCE-2, OBSERVANT, GAVS-II) were evaluated for the prediction of 30-day mortality. Observed 30-day mortality was 3.7% (TF 3.2%; TA 7.5%), mean 30-day mortality risk prediction varied from 5.8 ± 5.0% (OBSERVANT) to 23.4 ± 15.9% (LogES I). Discrimination performance (ROC analysis, c-indices) ranged from 0.60 (OBSERVANT) to 0.67 (STS PROM), without significant differences between models, between TF or TA approach or over time. STS PROM discriminated numerically best in TF TAVR (c-index 0.66; range of c-indices 0.60 to 0.66); performance was very similar in TA TAVR (LogES I, ES II, FRANCE-2 and GAVS-II all with c-index 0.67). Regarding calibration, all risk scoring models-especially LogES I-overestimated mortality risk, especially in high-risk patients., Conclusions: Surgical as well as TAVR-specific risk scoring models showed mediocre performance in prediction of 30-day mortality risk for TAVR in the German Rhine Transregio Aortic Diseases cohort. Development of new or updated risk models is necessary to improve risk stratification.

Background: Despite all efforts, mortality of out of hospital cardiac arrest (OHCA) remains high. Patients with OHCA due to a primary shockable rhythm typically have a better prognosis. However, outcome worsens if return of spontaneous circulation (ROSC) cannot be achieved quickly. There is insufficient evidence for maximum duration of resuscitation in these patients and it is unclear, which patients profit from transport under ongoing CPR., Objective: Investigate predictors for favourable neurologic outcome in OHCA patients with presumed cardiac cause due to refractory shockable rhythm (rSR)., Methods: Retrospective analysis of OHCA patients that presented to a tertiary hospital due to a rSR., Results: One hundred seventy-five OHCA patients with presumed cardiac cause due to rSR were included. Overall hospital mortality was 50% and 83% of initial survivors were discharged with a good neurologic outcome [cerebral performance category (CPC) 1-2]. In patients with a time from cardiac arrest to ROSC of > 45 min, 18% survived to CPC 1-2. Independent predictors for good neurologic outcome were age, lower no-flow time and lower serum lactate levels at hospital arrival., Conclusion: In an urban setting, a significant proportion of OHCA patients with rSR can survive to a good neurologic outcome, despite very long time to ROSC.

Objective: Residual paravalvular regurgitation (PVR) has been associated to adverse outcomes after transcatheter aortic valve replacement (TAVR). This study sought to evaluate the impact of device landing zone (DLZ) calcification on residual PVR after TAVR with different next-generation transcatheter heart valves., Methods: 642 patients underwent TAVR with a SAPIEN 3 (S3; n=292), ACURATE neo (NEO; n=166), Evolut R (ER; n=132) or Lotus (n=52). Extent, location and asymmetry of DLZ calcification were assessed from contrast-enhanced CT imaging and correlated to PVR at discharge., Results: PVR was ≥moderate in 0.7% of S3 patients, 9.6% of NEO patients, 9.8% of ER patients and 0% of Lotus patients (p<0.001), and these differences remained after matching for total DLZ calcium volume. The amount of DLZ calcium was significantly related to the degree of PVR in patients treated with S3 (p=0.045), NEO (p=0.004) and ER (p<0.001), but not in Lotus patients (p=0.698). The incidence of PVR ≥moderate increased significantly over the tertiles of DLZ calcium volume (p=0.046). On multivariable analysis, calcification of the aortic valve cusps, LVOT calcification and the use of self-expanding transcatheter aortic valve implantation (TAVI) prostheses emerged as predictors of PVR., Conclusions: The susceptibility to PVR depending on the amount of calcium was mainly observed in self-expanding TAVI prostheses. Thus, DLZ calcification is an important factor to be considered in prosthesis selection for each individual patient, keeping in mind the trade-off between PVR reduction, risk of new pacemaker implantation and unfavourable valve ha emodynamics., Competing Interests: Competing interests: FD received speakers honoraria from Boston Scientific. NS received travel compensation from Edwards and speakers honoraria and travel compensation from Boston Scientific. VR received speakers honoraria from Medtronic. TCWW and NM are proctors for Edwards. SB is a proctor for Edwards and received a research grant from Edwards. US is proctor for Edwards and Symetis SA and received research grants from Symetis SA and Edwards. TR is proctor for Boston Scientific and and received speakers honoraria from Edwards, Medtronic and Boston Scientific/Symetis., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Information on gender-related differences in terms of baseline characteristics and clinical outcome of patients undergoing MitraClip® implantation in daily clinical practice have been studied in smaller populations previously. This study sought to additionally evaluate gender-related differences in a larger German real-world patient population., Methods and Results: We analyzed data from the prospective and multicenter German TRAMI Registry. Between 08/2010 and 07/2013 327 women and 501 men underwent MitraClip® implantation for significant mitral valve regurgitation. Female patients were significantly older and showed higher rates of frailty compared to men. In contrast, men had significantly higher rates of comorbidities compared to women. The majority of patients underwent MitraClip® implantation for secondary mitral regurgitation, with no significant gender-related differences. MitraClip® treatment was equally effective in terms of procedural results and residual mitral regurgitation in women and men and complication rates were low. However, in this real-world analysis severe bleeding complications were significantly higher in women (p = .02) and re-intervention rates were significantly higher in men after MitraClip® treatment (p = .02). Women showed less improvement in functional NYHA class after MitraClip® treatment compared to men at 1-year follow-up (FU; p < .001). No significant differences between female and male patients were found in 1-year mortality and in re-hospitalization rates., Conclusion: In this analysis from a large prospective, multicenter real-world registry MitraClip® implantation is safe and effective for treatment of significant mitral regurgitation with equal postprocedural results and mortality rates during 1-year follow-up. Men and women showed a persisting and significant clinical benefit at 1-year FU after treatment. Complication and re-intervention rates were low. Additional studies are needed to further evaluate our findings on increased bleeding complications and decreased functional improvement in women at 1-year follow-up after MitraClip® therapy., (© 2019 Wiley Periodicals, Inc.)

Geriatric characteristics such as high age, multi-morbidity, polypharmacy and frailty are common in patients with atrial fibrillation (AF). In a retrospective study using a German claims database, effectiveness (ischaemic stroke/systemic embolism) and safety (intracerebral, gastrointestinal and major extracranial bleeding) were compared in patients with non-valvular AF starting non-vitamin K oral antagonists (NOACs) (apixaban, dabigatran and rivaroxaban) and phenprocoumon. Cox proportional hazards models were used to calculate adjusted hazard ratios, and interaction terms of the treatment group and geriatric status (defined by age ≥75 years, frailty, ≥ 4 co-morbidities and polypharmacy) were entered into the model. A total of 42,562 and 27,939 patients initiated NOAC and phenprocoumon treatment (mean age 74 years ± 11, 51% male) with a follow-up time of 147,785 person-years. Note that 52.9% of patients were elderly, 50.8% were frail, 37.0% were co-morbid and 46.5% had polypharmacy. NOAC use was not associated with effectiveness and gastrointestinal bleeding, neither in geriatric nor in non-geriatric patients. The hazard of major extracranial and intracranial bleeding was significantly decreased for NOAC use, with similar risk reduction in geriatric and non-geriatric patients: major extracranial bleeding 0.70 (95% confidence interval [CI], 0.56-0.87) to 0.73 (95% CI, 0.60-0.89) for the geriatric groups and 0.71 (95% CI, 0.56-0.93) to 0.76 (0.59-0.98) for the non-geriatric groups ( p -values for interaction > 0.6); and intracranial bleeding 0.52 (95% CI, 0.39-0.69) to 0.59 (95% CI, 0.47-0.73) for the geriatric groups and 0.54 (95% CI, 0.37-0.79) to 0.65 (95% CI, 0.49-0.86) for the non-geriatric groups ( p -values for interaction > 0.2). Hence, NOACs showed similar effectiveness and superior safety in geriatric and non-geriatric patients., Competing Interests: Dr. Hohmann has served as a consultant for Pfizer and received non-financial support from Orion Pharma, Actelion Pharma, Bayer and MSD. Professor Hohnloser has served as a consultant for Bayer, BMS/Pfizer, Boehringer-Ingelheim, Daiichi Sankyo and Jansen. Professor Pfister received lecture fees from Bayer, BMS/Pfizer and Daiichi Sankyo. Other authors report no conflict of interest.The authors have indicated that they have no other conflicts of interest regarding the content of this article., (Georg Thieme Verlag KG Stuttgart · New York.)

Background:  The latest generation of balloon-expandable valve, the Edwards Sapien 3 valve (S3V), was designed to reduce paravalvular regurgitation (PVR). We retrospectively compared S3V with Edwards Sapien XT valve (SXTV) with regard to postprocedural transvalvular pressure gradients (PGs)., Methods:  Analysis of 152 patients receiving SXTV and 125 patients receiving S3V between February 2009 and April 2015 was performed. Transvalvular PGs and the incidence and extent of aortic regurgitation (AR) were compared postprocedurally by echocardiography for each valve size., Results:  Postprocedurally, mean PGs for the 23 mm valves were 10.9 ± 5.3 versus 13.9 ± 5.1 ( p  = 0.017), whereas maximum PGs were 19.9 ± 8.3 versus 26.1 ± 10.4 mm Hg ( p  = 0.005) in SXTV and S3V patients, respectively. For the 26 mm valves, gradients were also significantly higher in S3V patients (mean PG: 11.6 ± 4.9 vs. 9.2 ± 4.2 [ p  = 0.004]; maximum PG: 23.0 ± 10.1 vs. 17.2 ± 7.4 mm Hg [ p  < 0.001]). Analysis revealed no significant differences in postprocedural transvalvular PGs for 29 mm valves (mean PG of 9.3 ± 3.9 and 11.2 ± 4.3 mm Hg [ p  = ns] and maximum PG of 17.5 ± 7.2 vs. 20.9 ± 6.8 mm Hg [ p  = ns]) between SXTV and S3V groups, respectively. With respect to PVR, the incidence of AR was significantly lower in S3V group ( p  = 0.001)., Conclusion:  S3V shows lower incidence of PVR; however, it is associated with significantly higher postprocedural transvalvular PGs for 23 and 26 mm valve sizes. These data might contribute to the scientific discussion, especially with respect to prosthesis selection in individual patients with small annular dimension., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag KG Stuttgart · New York.)

Aortic regurgitation is the consequence of a heterogenous alterations to the aortic valve and ascending aorta, respectively. Due to the widespread use of transcatheter aortic valve implantation, paravalvular leakage has gained interest as a special subtype of aortic regurgitation. The present article summarizes the current state and recent developments in the diagnostics and therapy of the different forms of aortic regurgitation., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: In contemporary practice with early catheterization in most patients with suspected acute myocardial infarction, the clinical utility of new or presumably new left bundle branch block (LBBB) as a diagnostic criterion equivalent to ST-segment elevation is not well established. This study therefore aimed to determine the predictive value of LBBB for the diagnosis of acute transmural myocardial infarction (or ST-segment elevation myocardial infarction, STEMI)., Patients and Methods: Between November 2006 and December 2011, 1,139 consecutive patients presenting to the heart center of the University of Cologne with suspected STEMI were examined. Of these patients, 935 presented with ST elevation, 72 with LBBB, and 132 had neither of these ECG changes. The diagnosis was confirmed with immediate coronary angiography., Results: Compared with ST-segment elevation, LBBB was associated with a higher prevalence of cardiovascular risk factors and end-organ damage, and more patients with LBBB presented with pulmonary edema or cardiogenic shock (Killip III/IV). STEMI was confirmed in 58.3 % of patients with LBBB and in 86.4 % with ST-segment elevation. The sensitivity (0.38 [0.29-0.46]; odds ratio: 1.24) and specificity (0.67 [0.58-0.77]) of LBBB for the prediction of STEMI were low. However, the additional assessment of troponin T (> 0.1 µg/l) increased the predictive value of LBBB significantly. After adjusting for age and gender, no difference in mortality was found between the groups., Conclusion: LBBB with acute chest pain characterizes a cohort of patients with high morbidity and mortality. For the triage of these patients at first contact, additional criteria should be evaluated, which could increase the specificity of LBBB for the diagnosis of STEMI.

Since 2008, the German Cardiac Society (DGK) has been establishing a network of certified chest pain units (CPUs). The goal of CPUs was and is to carry out differential diagnostics of acute or newly occurring chest pain of undetermined origin in a rapid and goal-oriented manner and to take immediate therapeutic measures. The basis for the previous certification process was criteria that have been established and published by the task force on CPUs. These criteria regulate the spatial and technical requirements and determine diagnostic and therapeutic strategies in patients with chest pain. Furthermore, the requirements for the organization of CPUs and the training requirements for the staff of a CPU are defined. The certification process is carried out by the DGK; currently, 225 CPUs are certified and 139 CPUs have been recertified after running for a period of 3 years. The certification criteria have now been revised and updated according to new guidelines.

Aims: Besides early percutaneous coronary intervention (PCI) long-term medical treatment is crucial for outcomes after ST-elevation myocardial infarction (STEMI). The present study aimed to identify predictors of adherence to evidence-based medication in this high risk population., Methods and Results: A total of 1025 consecutive patients with adjudicated STEMI treated by primary PCI in a single centre as part of the Cologne Infarction Model (KIM) were prospectively analysed. Gender-specific multivariate predictors of long-term medication adherence were identified. Follow-up with available information on drug use was completed for 610 of 738 (82.7%) patients confirmed to be alive after a median period of 36 months. Adherence was persistently high for evidence-based medication with 90.8% for acetylsalicylic acid (ASA), 88.2% for statins, 87.5% for beta-blockers and 79.2% for ACE-inhibitors or angiotensin-receptor blockers (ARBs). Patients with a history of heart failure had a higher medication adherence to beta-blockers, ACE-inhibitors/ARBs and diuretics, whereas long-term prescription rates for calcium channel blockers (CCBs) were lower in patients with reduced versus preserved ejection fraction. Patients with a history of hypertension presented higher medication adherence to CCBs, ACE-inhibitors/ARBs and diuretics but not to beta-blockers. On multivariate analysis, age, body mass index (BMI), hypertension, chronic kidney disease and lack of PCI were independently associated with prescription of diuretics at follow-up. In women, adherence was lower to beta-blockers and higher to CCBs compared to men., Conclusion: In the high risk population of STEMI patients long-term adherence to evidence-based medication is high. The lower adherence to beta-blockers and higher prescription rate for CCBs in women needs particular attention., (© The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Aims: This analysis from the German Mitral Valve Registry investigates the impact of the learning curve with the MitraClip(®) technique on procedural success and complications., Methods and Results: Consecutive patients treated since 2009 in centers that performed more than 50 transcatheter mitral repairs were included. Results of the first half of the patients were compared to those of the second. Altogether 496 patients from 10 centers were included. Patients treated later had less common severe heart failure symptoms (patients with NYHA IV: 22.1 vs. 14.5 %, p < 0.05). The EuroSCORE I (22.0 vs. 23.0 %, p = ns) and Society of Thoracic Surgeons (STS) score (7.5 vs. 9.5 %, p = ns) did not differ between both groups. Procedural success was 95.6 % (238/249) in the first cases and 94.7 % (232/245, p = ns) subsequently. Also procedural time (104.3 vs. 119 min, p = ns) and complications did not decrease over time., Conclusion: A learning curve using the MitraClip(®) device does not appear to significantly affect acute MR reduction, hospital and 30-day mortality. Most likely, the proctor system leads to already high initial procedure success and relatively short procedure time.

Objective: To evaluate in-hospital and short-term outcomes of percutaneous mitral valve repair according to patients' logistic EuroSCORE (logEuroSCORE) in a multicenter registry, Background: The logEuroSCORE is an established tool to predict the risk of mortality during cardiac surgery. In high-risk patients percutaneous mitral valve repair with the MitraClip system represents a less-invasive alternative, Methods: Data from 1002 patients, who underwent percutaneous mitral valve repair with the MitraClip system, were analyzed in the German Transcatheter Mitral Valve Interventions (TRAMI) Registry. A logEuroSCORE (mortality risk in %) ≥ 20 was considered high risk, Results: Of all patients, 557 (55.6%) had a logEuroSCORE ≥ 20. Implantation of the MitraClip was successful in 95.5 % (942/986) patients. Moderate residual mitral valve regurgitation was more often detected in patients with a logEuroSCORE ≥ 20 (23.8% vs. 17.1%, respectively, P < 0.05). In patients with a logEuroSCORE ≥ 20 the procedural complication rate was 8.9% (vs. 6.4, n.s.) and the in-hospital MACCE rate 4.9% (vs. 1.4% P < 0.01). The in-hospital mortality rate in patients with a logEuroSCORE ≥ 20 and logEuroSCORE < 20 was 4.3 and 1.1%, respectively (P ≤ 0.01) CONCLUSION: Percutaneous mitral valve repair with the MitraClip system is feasible in patients with a logEuroSCORE ≥ 20 with similar procedural results compared to patients with lower predicted risk. Although mortality was four times higher than in patients with logEuroSCORE < 20, mortality in high risk patients was lower than predicted. In those with a logEuroSCORE ≥ 20, moderate residual mitral valve regurgitation was more frequent., (© 2014 Wiley Periodicals, Inc.)

Background and Aim of the Study: Female gender has recently been suggested to predict a beneficial outcome and lower mortality following transcatheter aortic valve implantation (TAVI). The study aim was to address gender differences in outcome following TAVI and potentially to replicate these findings., Methods: The present single-center prospective registry of 326 patients with severe aortic stenosis treated by TAVI between 2008 and 2011 consisted of 181 women and 145 men., Results: The procedural risk was not significantly different between men and women at baseline. For all-cause mortality no difference was observed at 30 days and at 12 months after TAVI., Conclusion: While several baseline characteristics between men and women treated by TAVI were shown to be different among the study population, no difference was observed in survival between both genders.

Objectives: We report the results of a large single-center study evaluating predictors and outcomes after transcatheter aortic valve implantation (TAVI) with different devices and access routes according to the Valve Academic Research Consortium (VARC)., Background: The widespread adoption of TAVI warrants a systematic analysis of outcomes. Only few comprehensive data exist comparing different approaches as selected by a heart team., Methods: TAVI was performed in 326 consecutive patients (mean age 80.6 ± 7.1 years, 55.5% female) at high risk for surgery with balloon-expandable and self-expanding devices through transfemoral or transapical access. Data were analyzed according to VARC endpoints; predictors of mortality were identified., Results: All-cause mortality was 10.1% (30 days) and 29.9% (1 year) overall and comparable with regard to valve or access choice (P = 0.295) despite different risk profiles at baseline. Device success and 30-day safety endpoints were achieved in 87.1 and 21.2%. Myocardial infarction [hazard ratio (HR) 6.52], stage-2 and -3 acute kidney injury (HR 2.52 and 6.80) and major access site complications (HR 1.96) were independent predictors of 1-year all-cause mortality. Device success had a protective effect (HR 0.58). Baseline predictors included body mass index <20 kg/m(2) (HR 3.20), NYHA class IV (HR 1.87), left ventricular ejection-fraction <30% (HR 2.30), higher STS-PROM scores (HR 1.05 per percent), and age (group 75-85 years, HR 0.47)., Conclusions: Comparable results were achieved with different devices and access routes in a heart team approach. Baseline and perioperative predictors of all-cause mortality were identified, contributing to the refinement of patient and device selection criteria for TAVI., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: The incidence of vulvar squamous cell carcinomas located between the clitoris and urethra in young women is rising in distinct geographic regions, but characteristics of the tumors indicating certain carcinogenic mechanisms are unknown. The present study aimed at characterizing these vulvar cancers for their human papillomavirus (HPV), p16(INK4a), and p53 status, revealing potential pathways of carcinogenesis., Materials and Methods: Squamous cell vulvar cancers of the anterior fourchette were retrospectively collected from 8 German hospitals, with additional squamous cell cancers located at other sites of the vulva from 2 of the hospitals. All tumors were analyzed for HPV DNA by polymerase chain reaction and for p16(INK4a) and p53 expression by immunohistochemistry., Results: Potentially HPV-associated tumors (HPV and p16(INK4a) positive, 21.4% [27/126] of the anterior fourchette and 27.7% [13/47] from other locations), p53-overexpressing tumors (35.7% [45/126] and 29.8% [14/47]), and a third group (HPV/p16(INK4a) negative/p53 not overexpressed, 42.9% [54/126] and 42.6% [20/47]) were observed among tumors from the anterior fourchette as well as among vulvar cancers from other locations. Women with vulvar cancers of the anterior fourchette were of young age irrespective of the HPV/p16(INK4a)/p53 status., Conclusions: Different types of vulvar cancers can be found in squamous cell tumors of the anterior fourchette, similar to the finding in vulvar cancers from other locations and to what has previously been reported for vulvar squamous cell carcinomas in general.

Aims: To assess, and identify predictors of 2-year adverse outcomes of surgical high-risk patients after successful MitraClip therapy (MC), differentiated by the aetiology of mitral regurgitation (MR)., Methods and Results: Kaplan-Meier analysis was used to assess survival free from death, heart failure rehospitalization, and reintervention up to 2 years in 202 successfully treated patients [74 ± 9 years, 132 men (65%); secondary MR aetiology in 140 patients, primary MR in 62]. Predictors for study endpoints were determined using Cox regression analyses. Mortality was 20% at 1 year and 33% at 2 years in both primary and secondary MR patients; independent predictors of death were reduced forward stroke volume, impaired LV function, and renal failure in primary MR, yet only an increased logistic EuroSCORE in functional MR patients. The rate of rehospitalizations was not different between the patient subgroups for 6 months, but then diverged significantly in favour of primary MR patients (estimated 2-year incidence, primary MR 40% vs. secondary MR 66%). No predictor was found for primary MR patients, but increased LV end-diastolic volume significantly increased the risk of rehospitalization in functional MR patients. Reinterventions were overall rare (7.4% at 1 year, 9.7% at 2 years); primary MR patients required all except one reintervention within 2 months of MC, with again no predictors found, whereas secondary MR patients (all except one with discharge MR of 2+) exhibited a steadily declining freedom from reintervention curve throughout follow-up., Conclusion: MR aetiology affects rehospitalization and reintervention, but not mortality, differently after successful MC.

Aims: The influence of age on baseline demographics and outcomes of patients selected for MitraClip has not been previously investigated., Methods and Results: Baseline demographics and acute outcomes in 1,064 patients from the German TRAMI registry were stratified by age (525 patients ≥76 years and 539 patients <76 years). In elderly patients, logistic EuroSCORE was higher (25[15-40]% vs. 18[10-31]%, p<0.0001) and the proportion of women was greater (47.2% vs. 29.3%, p<0.0001). Elderly patients were more likely to have preserved left ventricular ejection fraction >50% (40.1% vs. 21.8%, p<0.0001) and degenerative mitral regurgitation (DMR, 35.3% vs. 25.6%, p<0.01). Age was the most frequent reason for non-surgical treatment in the elderly (69.4% vs. 36.1%, p<0.0001). The intrahospital MACCE (death, myocardial infarction, stroke) was low in both groups (3.5% vs. 3.4%, p=0.93) and the proportion of non-severe mitral regurgitation at discharge was similar (95.8% vs. 96.4%, p=0.73). A logistic regression model did not reveal any significant impact of age on acute efficacy and safety of MitraClip therapy. In both groups, the majority of patients were discharged home (81.8% vs. 86.2%, p=0.06)., Conclusions: Elderly and younger patients have similar benefits from MitraClip therapy. Age was the most frequent cause for denying surgery in elderly patients.

Purpose: Transcardiopulmonary thermodilution (TPTD, SVTD) as well as calibrated (SVPC CAL) and uncalibrated (SVPC UNCAL) arterial pulse contour analysis (PC) are increasingly promoted as less-invasive technologies to measure stroke volume (SV) but their reliability in aortic valve disease was unknown. The objective of this prospective study was to investigate the validity of three less-invasive techniques to assess SV in conditions involving aortic stenosis (AS) and valvuloplasty-induced aortic insufficiency (AI) compared with transesophageal echocardiography., Methods: In 18 patients undergoing transcatheter aortic valve implantation, SVTD and SVPC CAL were determined using a central pressure signal via the brachial artery and SVPC UNCAL using a peripheral radial signal., Results: In aortic valve dysfunction TPTD achieved adequate reproducibility (concordance correlation coefficient (CCC): AS 0.84; AI 0.82) and agreement (percentage error (PE): AS 26.3 %; AI 26.2 %) with the reference technique. In severe AS, SVPC CAL (PE 25.7 %; CCC 0.85) but not SVPC UNCAL (PE 50.4 %; CCC 0.38) was reliable. Neither calibrated nor uncalibrated PC (SVPC CAL: PE 51.5 %; CCC 0.49; SVPC UNCAL: PE 61.9 %; CCC 0.22) was valid in AI. Trending ability to hemodynamic changes, quantified by the ΔSV vector and the angle θ, was acceptable for each measurement modality., Conclusions: Transcardiopulmonary thermodilution is valid in aortic valve dysfunction. Calibration of PC substantially improves reliability in aortic valve disease. Calibrated PC is valid in severe AS. Valvuloplasty-induced AI seriously confounds PC measurements. In uncalibrated PC approaches, the relative SV trend is superior to single absolute values.

Objective: To evaluate mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-atrial natriuretic peptide (MR-proANP) as prognostic biomarkers in a representative 'real world' cohort of patients with suspected acute coronary syndrome (ACS)., Design: Prospective observational multicentre cohort study., Setting: Chest pain units of three major hospitals in Germany from 2007 to 2008., Patients: Patients presenting with signs and symptoms suggestive of an ACS., Main Outcome Measures: Primary end point was death or non-fatal myocardial infarction (MI), and secondary end point was death, non-fatal MI, stroke, need for coronary revascularisation, and hospital admission for cardiovascular cause or acute heart failure within 6 months after enrolment., Results: 1386 patients (male/female = 920/466) were enrolled. Follow-up information was available for 97.8% of patients (median follow-up time 183 days). Forty-three patients reached the primary end point, and 132 the secondary end point. Patients who reached a primary end point had significantly higher MR-proANP (271 vs 101 pmol/l, p < 0.001) and MR-proADM (0.86 vs 0.59 nmol/l, p < 0.001) concentrations than those who did not. Cox regression analysis revealed a 2.55-fold risk of death or non fatal MI (95% CI 1.48 to 2.46, p < 0.001) for an increment of the log-transformed MR-proANP concentration by 1 SD after adjustment for cardiovascular risk factors, and a 1.91-fold risk (95% CI 1.48 to 2.46, p < 0.001) for MR-proADM. Both peptides could result in significant reclassification of patients when added to the Global Registry of Acute Coronary Events risk score, with an overall net reclassification improvement of 41.2% for MR-proADM and 35.7% for MR-proANP., Conclusions: MR-proADM and MR-proANP are predictors of future cardiovascular events in patients presenting with acute chest pain and might facilitate the choice of treatment in those patients complementary to established risk scores.

The indication for antiviral treatment of patients with chronic hepatitis B is based on serum HBV DNA levels, transaminases, and histological grade and stage. The relation of liver fibrosis and inflammation to ALT activity in chronic hepatitis B infection was investigated in a nonendemic, European setting. A total of 253 patients with chronic hepatitis B who had undergone liver biopsy at the Clinic of Gastroenterology, Hepatology, and Infectious Diseases, Düsseldorf,Germany over the past 19 years (1990–2009) were evaluated. Thirty-nine patients had persistently normal transaminases, 86 patients had ALT with 1–2 x ULN (upper limit of normal) and 128 patients had ALT >2 x ULN. Liver fibrosis or inflammation was defined as significant for stages or grades ≥ 2 according to the Desmet/Scheuer score. Significant liver fibrosis (F ≥ 2)was found in 36%, cirrhosis in 18%, and significant inflammation (G ≥ 2) in 27% of patients with normal transaminases. There was no difference in the stage of liver fibrosis and the frequency of cirrhosis between patients with normal and elevated transaminases. The most important factor associated with the presence of cirrhosis in multivariate analysis was age ≥ 40 years (P < 0.003). If concomitant factors like elevated GGT or male sex were furthermore present high prevalences of significant liver disease were found. The data indicate that, in a European setting, patients with chronic hepatitis B infection, and normal transaminases frequently have significant liver fibrosis or cirrhosis.Therefore, liver biopsy or liver stiffness measurement (LSM) should be performed in these patients to determine the stage of liver fibrosis., (Copyright © 2011 Wiley-Liss, Inc.)

Purpose: To characterize the prognostic and predictive impact of protein expression profiles in high-risk breast cancer patients who had previously been shown to benefit from high-dose chemotherapy (HDCT) in comparison to dose-dense chemotherapy (DDCT)., Experimental Design: The expression of 34 protein markers was evaluated using tissue microarrays containing paraffin-embedded breast cancer samples from 236 patients who were randomized to the West German Study Group AM01 trial., Results: (a) 24 protein markers of the initial panel of 34 markers were sufficient to identify five profile clusters (subtypes) by K-means clustering: luminal-A (27%), luminal-B (12%), HER-2 (21%), basal-like (13%) cluster, and a so-called "multiple marker negative" (MMN) cluster (27%) characterized by the absence of specifying markers. (b) After DDCT, HER-2 and basal-like groups had significantly worse event-free survival [EFS; hazard ratio (HR), 3.6 [95% confidence interval (95% CI), 1.65-8.18; P = 0.001] and HR, 3.7 (95% CI, 1.68-8.48; P < 0.0001), respectively] when compared with both luminal groups. (c) After HDCT, the HR was 1.5 (95% CI, 0.76-3.05) for EFS in the HER-2 subgroup and 1.1 (95% CI, 0.37-3.32) in the basal-like subgroup, which indicates a better outcome for patients in the HER-2 and basal-like subgroups who received HDCT. The MMN cluster showed a trend to a better EFS after HDCT compared with DDCT., Conclusions: Protein expression profiling in high-risk breast cancers identified five subtypes, which differed with respect to survival and response to chemotherapy: In contrast to luminal-A and luminal-B subtypes, HER-2 and basal-like subgroups had a significant predictive benefit, and the MMN cluster had a trend to a predictive benefit, both from HDCT when compared with DDCT.

As representatives of low and high incidence countries respectively, 72 esophageal squamous cell carcinomas and 40 adenocarcinomas from Germany, and 43 esophageal squamous cell carcinomas from Russia were tested for the presence of Epstein-Barr virus (EBV) DNA by PCR and in situ hybridization. Thirty-four percent of the squamous cell carcinomas (SCC) and 26% of the adenocarcinomas (AC) contained EBV DNA as detected by nested PCR. Quantitative analysis using real time PCR revealed one copy of the EBV genome per every 27-200,000 cells. EBER RNA in situ hybridization showed no EBV-specific transcripts in the nuclei of the tumor cells. However, EBER transcripts were expressed in the nuclei of tumor infiltrating lymphocytes in 7 SCC and 1 AC of 24 EBV DNA positive cases. The present data provide no evidence for the persistence of EBV in the tumor cells of esophageal cancer. In contrast to a previous report from Taiwan, EBV is unlikely to play a role in esophageal carcinogenesis.