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A novel echocardiography-based definition of atrial functional tricuspid regurgitation (A-FTR) has shown superior outcomes in patients undergoing conservative treatment or tricuspid valve transcatheter edge-to-edge repair. Its prognostic significance for transcatheter tricuspid valve annuloplasty (TTVA) outcomes is unknown. This study sought to investigate prognostic, clinical, and technical implications of A-FTR phenotype in patients undergoing TTVA. This multicenter study investigated clinical and echocardiographic outcomes up to 1 year in 165 consecutive patients who underwent TTVA for A-FTR (characterized by the absence of tricuspid valve tenting, midventricular right ventricular [RV] dilatation, and impaired left ventricular ejection fraction) and nonatrial functional tricuspid regurgitation (NA-FTR). A total of 62 A-FTR and 103 NA-FTR patients were identified, with the latter exhibiting more pronounced RV remodeling. Compared to baseline, the tricuspid regurgitation (TR) grade at discharge was significantly reduced (P < 0.001 for both subtypes), and TR ≤II was achieved more frequently in A-FTR (85.2% vs 60.8%; P = 0.001). Baseline TR grade and A-FTR phenotype were independently associated with TR ≤II at discharge and 30 days. In multivariate analyses, A-FTR phenotype was a strong predictor (OR: 5.8; 95% CI: 2.1-16.1; P < 0.001) of TR ≤II at 30 days. At 1 year, functional class had significantly improved compared to baseline (both P < 0.001). One-year mortality was lower in A-FTR (6.5% vs 23.8%; P = 0.011) without significant differences in heart failure hospitalizations (13.3% vs 22.7%; P = 0.188). Direct TTVA effectively reduces TR in both A-FTR, which is a strong and independent predictor of achieving TR ≤II, and NA-FTR. Even though NA-FTR showed more RV remodeling at baseline, both phenotypes experienced similar symptomatic improvement, emphasizing the benefit of TTVA even in advanced disease stages. Additionally, phenotyping was of prognostic relevance in patients undergoing TTVA. [Display omitted] [ABSTRACT FROM AUTHOR]

Mitral transcatheter edge-to-edge repair (M-TEER) is a guideline-recommended treatment option for patients with severe symptomatic mitral regurgitation (MR). Outcomes with the PASCAL system in a post-market setting have not been established. The authors report 30-day and 1-year outcomes from the MiCLASP (Transcatheter Repair of Mitral Regurgitation with Edwards PASCAL Transcatheter Valve Repair System) European post-market clinical follow-up study. Patients with symptomatic, clinically significant MR were prospectively enrolled. The primary safety endpoint was clinical events committee–adjudicated 30-day composite major adverse event rate and the primary effectiveness endpoint was echocardiographic core laboratory–assessed MR severity at discharge compared with baseline. Clinical, echocardiographic, functional, and quality-of-life outcomes were assessed at 1 year. A total of 544 patients were enrolled (59% functional MR, 30% degenerative MR). The 30-day composite major adverse event rate was 6.8%. MR reduction was significant from baseline to discharge and sustained at 1 year with 98% of patients achieving MR ≤2+ and 82.6% MR ≤1+ (all P < 0.001 vs baseline). One-year Kaplan-Meier estimate for survival was 87.3%, and freedom from heart failure hospitalization was 84.3%. Significant functional and quality-of-life improvements were observed at 1 year, including 71.6% in NYHA functional class I/II, 14.4-point increase in Kansas City Cardiomyopathy Questionnaire score, and 24.2-m improvement in 6-minute walk distance (all P < 0.001 vs baseline). One-year outcomes of this large cohort from the MiCLASP study demonstrate continued safety and effectiveness of M-TEER with the PASCAL system in a post-market setting. Results demonstrate high survival and freedom from heart failure hospitalization, significant and sustained MR reduction, and improvements in symptoms, functional capacity, and quality of life. [Display omitted] [ABSTRACT FROM AUTHOR]

Early studies of the Tendyne transcatheter mitral valve replacement (TMVR) showed promising results in a small selective cohort. The authors present 1-year data from the currently largest commercial, real-world cohort originating from the investigator-initiated TENDER (Tendyne European Experience) registry. All patients from the TENDER registry eligible for 1-year follow-up were included. The primary safety endpoint was 1-year cardiovascular mortality. Primary performance endpoint was reduction of mitral regurgitation (MR) up to 1 year. Among 195 eligible patients undergoing TMVR (median age 77 years [Q1-Q3: 71-81 years], 60% men, median Society of Thoracic Surgeons Predicted Risk of Mortality 5.6% [Q1-Q3: 3.6%-8.9%], 81% in NYHA functional class III or IV, 94% with MR 3+/4+), 31% had "real-world" indications for TMVR (severe mitral annular calcification, prior mitral valve treatment, or others) outside of the instructions for use. The technical success rate was 95%. The cardiovascular mortality rate was 7% at 30 day and 17% at 1 year (all-cause mortality rates were 9% and 29%, respectively). Reintervention or surgery following discharge was 4%, while rates of heart failure hospitalization reduced from 68% in the preceding year to 25% during 1-year follow-up. Durable MR reduction to ≤1+ was achieved in 98% of patients, and at 1 year, 83% were in NYHA functional class I or II. There was no difference in survival and major adverse events between on-label use and "real-world" indications up to 1 year. This large, real-world, observational registry reports high technical success, durable and complete MR elimination, significant clinical benefits, and a 1-year cardiovascular mortality rate of 17% after Tendyne TMVR. Outcomes were comparable between on-label use and "real-world" indications, offering a safe and efficacious treatment option for patients without alternative treatments. (Tendyne European Experience Registry [TENDER]; NCT04898335) [Display omitted] [ABSTRACT FROM AUTHOR]

Patients with severe aortic regurgitation (AR) are often not considered for surgery because of increased surgical risk. Because of unique anatomical characteristics among patients with AR, interventional treatment options are limited, and implantation results are inconsistent compared with those among patients with aortic stenosis. The authors describe the initial commercial experience of the first Conformité Européenne–marked transfemoral transcatheter aortic valve replacement system (JenaValve Trilogy [JV]) for the treatment of patients with AR. This multicenter registry included 58 consecutive patients from 6 centers across Germany. Transcatheter aortic valve replacement was performed with the JV system for isolated severe and symptomatic AR. Patient characteristics, primary implantation outcomes, and valve performance up to 30 days were analyzed using Valve Academic Research Consortium 3 definitions. The mean patient age was 76.5 ± 9 years, with a mean Society of Thoracic Surgeons score of 4.2% ± 4.3%. Device success was achieved in 98% of patients. The mean gradient was 4.3 ± 1.6 mm Hg, and no moderate or severe paravalvular regurgitation occurred. No conversion to open heart surgery or valve embolization was reported. There were no major vascular complications or bleeding events. The rate of new permanent pacemaker implantation was 19.6%. At 30 days, 92% of the patients were in NYHA functional class I or II, and the 30-day mortality rate was 1.7%. Treatment of patients with severe symptomatic AR using the transfemoral JV system is safe and effective. Given its favorable hemodynamic performance and low complication rates, this system may offer a new treatment option for patients with AR not suitable for surgery. [Display omitted] [ABSTRACT FROM AUTHOR]

Men and women differ regarding comorbidities, pathophysiology, and the progression of valvular heart diseases. This study sought to assess sex-related differences regarding clinical characteristics and the outcome of patients with severe tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve intervention (TTVI). All 702 patients in this multicenter study underwent TTVI for severe TR. The primary outcome was 2-year all-cause mortality. Among 386 women and 316 men in this study, men were more often diagnosed with coronary artery disease (52.9% in men vs 35.5% in women; P = 5.6 × 10−6). Subsequently, the underlying etiology for TR in men was predominantly secondary ventricular (64.6% in men vs 50.0% in women; P = 1.4 × 10−4), whereas women more often presented with secondary atrial etiology (41.7% in women vs 24.4% in men, P = 2.0 × 10−6). Notably, 2-year survival after TTVI was similar in women and men (69.9% in women vs 63.7% in men; P = 0.144). Multivariate regression analysis identified dyspnea expressed as New York Heart Association functional class, tricuspid annulus plane systolic excursion (TAPSE), and mean pulmonary artery pressure (mPAP) as independent predictors for 2-year mortality. The prognostic significance of TAPSE and mPAP differed between sexes. Consequently, we looked at right ventricular–pulmonary arterial coupling expressed as TAPSE/mPAP and identified sex-specific thresholds to best predict survival; women with a TAPSE/mPAP ratio <0.612 mm/mm Hg displayed a 3.43-fold increased HR for 2-year mortality (P < 0.001), whereas men with a TAPSE/mPAP ratio <0.434 mm/mm Hg displayed a 2.05-fold increased HR for 2-year mortality (P = 0.001). Even though men and women differ in the etiology of TR, both sexes show similar survival rates after TTVI. The TAPSE/mPAP ratio can improve prognostication after TTVI, and sex-specific thresholds should be applied to guide future patient selection. [Display omitted] [ABSTRACT FROM AUTHOR]

Guideline-directed medical therapy (GDMT) optimization is mandatory before transcatheter edge-to-edge mitral valve repair (M-TEER) in patients with secondary mitral regurgitation (SMR) and heart failure (HF) with reduced ejection fraction (HFrEF). However, the effect of M-TEER on GDMT is unknown. The authors sought to evaluate frequency, prognostic implications and predictors of GDMT uptitration after M-TEER in patients with SMR and HFrEF. This is a retrospective analysis of prospectively collected data from the EuroSMR Registry. The primary events were all-cause death and the composite of all-cause death or HF hospitalization. Among the 1,641 EuroSMR patients, 810 had full datasets regarding GDMT and were included in this study. GDMT uptitration occurred in 307 patients (38%) after M-TEER. Proportion of patients receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists was 78%, 89%, and 62% before M-TEER and 84%, 91%, and 66% 6 months after M-TEER (all P < 0.001). Patients with GDMT uptitration had a lower risk of all-cause death (adjusted HR: 0.62; 95% CI: 0.41-0.93; P = 0.020) and of all-cause death or HF hospitalization (adjusted HR: 0.54; 95% CI: 0.38-0.76; P < 0.001) compared with those without. Degree of MR reduction between baseline and 6-month follow-up was an independent predictor of GDMT uptitration after M-TEER (adjusted OR: 1.71; 95% CI: 1.08-2.71; P = 0.022). GDMT uptitration after M-TEER occurred in a considerable proportion of patients with SMR and HFrEF and is independently associated with lower rates for mortality and HF hospitalizations. A greater decrease in MR was associated with increased likelihood for GDMT uptitration. [Display omitted] [ABSTRACT FROM AUTHOR]

Leaflet morphology has been associated with treatment success in edge-to-edge repair of tricuspid regurgitation (TR), but the impact on annuloplasty is unclear. The authors sought to examine the association of leaflet morphology with efficacy and safety of direct annuloplasty in TR. The authors analyzed patients who underwent catheter-based direct annuloplasty with the Cardioband at 3 centers. Leaflet morphology was assessed according to number and location of leaflets by echocardiography. Patients with simple morphology (2 or 3 leaflets) were compared with complex morphology (>3 leaflets). The study included 120 patients (median age 80 years) with ≥severe TR. A total of 48.3% of patients had a 3-leaflet morphology, 5% a 2-leaflet morphology, and 46.7% had >3 tricuspid leaflets. Baseline characteristics did not differ relevantly between groups except for a higher incidence of torrential TR grade (50 vs 26.6%) in complex morphologies. Postprocedural improvement of 1 (90.6% vs 92.9%) and 2 (71.9% vs 67.9%) TR grades was not significantly different between groups, but patients with complex morphology had more often residual TR ≥3 at discharge (48.2 vs 26.6%; P = 0.014). This difference did not remain significant (P = 0.112) after adjusting for baseline TR severity, coaptation gap, and nonanterior jet localization. Safety endpoints including complications of the right coronary artery, and technical success did not show significant differences. Efficacy and safety of transcatheter direct annuloplasty using Cardioband are not affected by leaflet morphology. Assessment of leaflet morphology should be part of procedural planning in patients with TR and might help to individually tailor repair techniques to patient anatomy. [Display omitted] [ABSTRACT FROM AUTHOR]

Secondary mitral regurgitation (SMR) is a progressive disease with characteristic pathophysiological changes that may influence prognosis. Although the staging of SMR patients suffering from heart failure with reduced ejection fraction (HFrEF) according to extramitral cardiac involvement has prognostic value in medically treated patients, such data are so far lacking for edge-to-edge mitral valve repair (M-TEER). This study sought to classify M-TEER patients into disease stages based on the phenotype of extramitral cardiac involvement and to assess its impact on symptomatic and survival outcomes. Based on echocardiographic and clinical assessment, patients were assigned to 1 of the following HFrEF-SMR groups: left ventricular involvement (Stage 1), left atrial involvement (Stage 2), right ventricular volume/pressure overload (Stage 3), or biventricular failure (Stage 4). A Cox regression model was implemented to investigate the impact of HFrEF-SMR stages on 2-year all-cause mortality. The symptomatic outcome was assessed with New York Heart Association functional class at follow-up. Among a total of 849 eligible patients who underwent M-TEER for relevant SMR from 2008 until 2019, 9.5% (n = 81) presented with left ventricular involvement, 46% (n = 393) with left atrial involvement, 15% (n = 129) with right ventricular pressure/volume overload, and 29% (n = 246) with biventricular failure. An increase in HFrEF-SMR stage was associated with increased 2-year all-cause mortality after M-TEER (HR: 1.39; CI: 1.23-1.58; P < 0.01). Furthermore, higher HFrEF-SMR stages were associated with significantly less symptomatic improvement at follow-up. The classification of M-TEER patients into HFrEF-SMR stages according to extramitral cardiac involvement provides prognostic value in terms of postinterventional survival and symptomatic improvement. [Display omitted] [ABSTRACT FROM AUTHOR]

This study aimed to improve echocardiographic assessment of pulmonary hypertension (PH) in patients presenting with severe tricuspid regurgitation (TR). Echocardiographic assessment of PH in patients with severe TR carries several pitfalls for underestimation, hence concealing the true severity of PH in very sick patients in particular, and ultimately obscuring the impact of PH on survival after transcatheter tricuspid valve intervention (TTVI). All patients in this study underwent TTVI for severe TR between 2016 and 2020. To predict the mean pulmonary artery pressure (mPAP) solely based on echocardiographic parameters, we trained an extreme gradient boosting (XGB) algorithm. The derivation cohort was constituted by 116 out of 162 patients with both echocardiography and right heart catheterization data, preprocedurally obtained, from a bicentric registry. Moreover, 142 patients from an independent institution served for external validation. Systolic pulmonary artery pressure was consistently underestimated by echocardiography in comparison to right heart catheterization (40.3 ± 15.9 mm Hg vs 44.1 ± 12.9 mm Hg; P = 0.0066), and the assessment was most discrepant among patients with severe defects of the tricuspid valve and impaired right ventricular systolic function. Using 9 echocardiographic parameters as input variables, an XGB algorithm could reliably predict mPAP levels (R = 0.96, P < 2.2 × 10-16). Moreover, patients with elevations in predicted mPAP levels ≥29.9 mm Hg showed significantly reduced 2-year survival after TTVI (58.3% [95% CI: 41.7%-81.6%] vs 78.8% [95% CI: 68.7%-90.5%]; P = 0.026). Importantly, the poor prognosis associated with elevation in predicted mPAP levels was externally confirmed (HR for 2-year mortality: 2.9 [95% CI: 1.5-5.7]; P = 0.002). PH in patients with severe TR can be reliably assessed based on echocardiographic parameters in conjunction with an XGB algorithm, and elevations in predicted mPAP levels translate into increased mortality after TTVI. [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of this study was to develop a machine learning (ML)–based risk stratification tool for 1-year mortality in transcatheter mitral valve repair (TMVR) patients incorporating metabolic and hemodynamic parameters. The lack of appropriate, well-validated, and specific means to risk-stratify patients with mitral regurgitation complicates the evaluation of prognostic benefits of TMVR in clinical trials and practice. A total of 1,009 TMVR patients from 3 university hospitals within the Heart Failure Network Rhineland were included; 1 hospital (n = 317) served as external validation. The primary endpoint was all-cause 1-year mortality. Model performance was assessed using receiver-operating characteristic curve analysis. In the derivation cohort, different ML algorithms were tested using 5-fold cross-validation. The final model, called MITRALITY (transcatheter mitral valve repair mortality prediction system) was tested in the validation cohort with respect to existing clinical scores. Extreme gradient boosting was selected for the MITRALITY score, using only 6 baseline clinical features for prediction (in order of predictive importance): urea, hemoglobin, N-terminal pro–brain natriuretic peptide, mean arterial pressure, body mass index, and creatinine. In the external validation cohort, the MITRALITY score's area under the curve was 0.783 (95% CI: 0.716-0.849), while existing scores yielded areas under the curve of 0.721 (95% CI: 0.63-0.811) and 0.657 (95% CI: 0.536-0.778) at best. The MITRALITY score is a novel, internally and externally validated ML-based tool for risk stratification of patients prior to TMVR, potentially serving future clinical trials and daily clinical practice. [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the impact of residual mitral regurgitation (resMR) on mortality with respect to left ventricular dilatation (LV-Dil) or right ventricular dysfunction (RV-Dys) in patients with secondary mitral regurgitation (SMR) who underwent mitral valve transcatheter edge-to-edge repair (TEER). The presence of LV-Dil and RV-Dys correlates with advanced stages of heart failure in SMR patients, which may impact the outcome after TEER. SMR patients in a European multicenter registry were evaluated. Investigated outcomes were 2-year all-cause mortality and improvement in New York Heart Association functional class with respect to MR reduction, LV-Dil (defined as LV end-diastolic volume ≥159 ml), and RV-Dys (defined as tricuspid annular plane systolic excursion-to-systolic pulmonary artery pressure ratio of <0.274 mm/mm Hg). Among 809 included patients, resMR ≤1+ was achieved in 546 (67%) patients. Overall estimated 2-year mortality rate was 32%. Post-procedural resMR was significantly associated with mortality (p = 0.031). Although the improvement in New York Heart Association functional class persisted regardless of either LV-Dil or RV-Dys, the beneficial treatment effect of resMR ≤1+ on 2-year mortality was observed only in patients without LV-Dil and RV-Dys (hazard ratio: 1.75; 95% confidence interval: 1.03 to 3.00). Achieving optimal MR reduction by TEER is associated with improved survival in SMR patients, especially if the progress in heart failure is not too advanced. In SMR patients with advanced stages of heart failure, as evidenced by LV-Dil or RV-Dys, the treatment effect of TEER on symptomatic improvement is maintained, but the survival benefit appears to be reduced. [Display omitted] [ABSTRACT FROM AUTHOR]

The authors sought to assess sex-based differences in characteristics and outcomes of patients undergoing transcatheter edge-to-edge mitral valve repair (TMVR) for secondary mitral regurgitation (SMR). Subgroup analysis from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial indicated potential sex-related differences in outcomes after TMVR. The impact of sex on results after TMVR in a real-world setting is unknown. The authors assessed clinical outcomes and echocardiographic parameters in women and men undergoing TMVR for SMR between 2008 and 2018 who were included in the large, international, multicenter real-world EuroSMR registry (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation). A total of 1,233 patients, including 445 women (36%) and 788 men (64%), were analyzed. Although women were significantly older and had fewer comorbidities than men, TMVR was equally effective in women and men (mitral regurgitation [MR] grade ≤2+ at discharge: 93.2% vs. 94.6% for women vs. men; p = 0.35). All-cause mortality at 1 year (17.9% vs. 18.9%, adjusted hazard ratio: 0.806; p = 0.46) and at 2-year follow-up (26.5% vs. 26.4%, adjusted hazard ratio: 0.757; p = 0.26) were similar in women versus men after multivariate regression analysis. Durability of MR reduction, improvement in symptoms, quality of life, and functional capacity did also not differ during follow-up. Results from the EuroSMR registry confirmed effective and similar MR reduction with TMVR in women and men. There were no sex-related differences in clinical outcomes up to 2 years of follow-up. [Display omitted] [ABSTRACT FROM AUTHOR]

This study sought to assess the impact of right ventricular dysfunction (RVD) as defined by impaired right ventricular-to-pulmonary artery (RV-PA) coupling, on survival after edge-to-edge transcatheter mitral valve repair (TMVR) for severe secondary mitral regurgitation (SMR). Conflicting data exist regarding the benefit of TMVR in severe SMR. A possible explanation could be differences in RVD. Using data from the EuroSMR (European Registry on Outcomes in Secondary Mitral Regurgitation) registry, this study compared the characteristics and outcomes of SMR patients undergoing TMVR, according to their RV-PA coupling, assessed by tricuspid annular plane systolic excursion-to-systolic pulmonary artery pressure (TAPSE/sPAP) ratio. Overall, 817 patients with severe SMR and available RV-PA coupling assessment underwent TMVR in the participating centers. RVD was present in 211 patients (25.8% with a TAPSE/sPAP ratio <0.274 mm/mm Hg). Although all patients demonstrated significant improvement in their New York Heart Association (NYHA) functional class, there was a trend toward a lower rate of NYHA functional class I or II among patients with RVD (56.5% vs. 65.5%, respectively; p = 0.086) after TMVR. Survival rates at 1 and 2 years were lower among patients with RVD (70.2% vs. 84.0%, respectively; p < 0.001; and 53.4% vs. 73.1%, respectively; p < 0.001). On multivariate analysis, a reduced TAPSE/sPAP ratio was a strong predictor of mortality (odds ratio: 1.62; 95% confidence interval: 1.14 to 2.31; p = 0.007). RVD, as shown by impairment of RV-PA coupling, is a major predictor of adverse outcome in patients undergoing TMVR for severe SMR. The often neglected functional and anatomic RV parameters should be systematically assessed when planning TMVR procedures for patients with severe SMR. [Display omitted] [ABSTRACT FROM AUTHOR]

The purpose of this paper was to evaluate the impact of proportionality of secondary mitral regurgitation (SMR) in a large real-world registry of transcatheter edge-to-edge mitral valve repair (TMVr) Differences in the outcomes of recent randomized trials of TMVr for SMR may be explained by the proportionality of SMR severity to left ventricular (LV) volume. The ratio of pre-procedural effective regurgitant orifice area (EROA) to LV end-diastolic volume (LVEDV) was retrospectively assessed in patients undergoing TMVr for severe SMR between 2008 and 2019 from the EuroSMR registry. A recently proposed SMR proportionality scheme was adapted to stratify patients according to EROA/LVEDV ratio in 3 groups: MR-dominant (MD), MR-LV-co-dominant (MLCD), and LV-dominant (LD). All-cause mortality was assessed as a primary outcome, secondary heart failure (HF) outcomes included hospitalization for HF (HHF), New York Heart Association (NYHA) functional class, N-terminal pro–B-type natriuretic peptide (NT-proBNP), 6-min-walk distance, quality of life and MR grade. A total of 1,016 patients with an EROA/LVEDV ratio were followed for 22 months after TMVr. MR was reduced to grade ≤2+ in 92%, 96%, and 94% of patients (for MD, MLCD, and LD, respectively; p = 0.18). After adjustment for covariates including age, sex, diabetes, kidney function, body surface area, LV ejection fraction, and procedural MR reduction (grade ≤2+), adjusted rates of 2-year mortality in MD patients did not differ from those for MLCD patients (17% vs. 18%, respectively), whereas it was higher in LD patients (23%; p = 0.02 for comparison vs. MD+MLCD). The adjusted first HHF rate differed between groups (44% in MD, 56% in MLCD, 29% in LD; p = 0.01) as did the adjusted time for first death or HHF rate (66% in MD, 82% in MLCD, 68% in LD; p = 0.02). Improvement of NYHA functional class was seen in all groups (p < 0.001). Values for 6-min-walk distances, quality of life and NT-proBNP improved in most patients. MD and MLCD patients had a comparable, adjusted 2-year mortality rate after TMVr which was slightly better than that of LD patients. Patients treated with TMVr had symptomatic improvement regardless of EROA/LVEDV ratio. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: In acute myocardial infarction complicated by cardiogenic shock the use of mechanical circulatory support devices remains controversial and data from randomized clinical trials are very limited. Extracorporeal life support (ECLS) - venoarterial extracorporeal membrane oxygenation - provides the strongest hemodynamic support in addition to oxygenation. However, despite increasing use it has not yet been properly investigated in randomized trials. Therefore, a prospective randomized adequately powered clinical trial is warranted.Study Design: The ECLS-SHOCK trial is a 420-patient controlled, international, multicenter, randomized, open-label trial. It is designed to compare whether treatment with ECLS in addition to early revascularization with percutaneous coronary intervention or alternatively coronary artery bypass grafting and optimal medical treatment is beneficial in comparison to no-ECLS in patients with severe infarct-related cardiogenic shock. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoint of ECLS-SHOCK is 30-day mortality. Secondary outcome measures such as hemodynamic, laboratory, and clinical parameters will serve as surrogate endpoints for prognosis. Furthermore, a longer follow-up at 6 and 12 months will be performed including quality of life assessment. Safety endpoints include peripheral ischemic vascular complications, bleeding and stroke.Conclusions: The ECLS-SHOCK trial will address essential questions of efficacy and safety of ECLS in addition to early revascularization in acute myocardial infarction complicated by cardiogenic shock. [ABSTRACT FROM AUTHOR]

The aim of this study was to retrospectively compare the characteristics, procedural courses, and outcomes of patients presenting with concomitant mitral regurgitation (MR) and tricuspid regurgitation (TR) in the TriValve (Transcatheter Tricuspid Valve Therapies) and TRAMI (Transcatheter Mitral Valve Interventions) registries. Transcatheter mitral edge-to-edge valve repair (TMVR) has been shown to be successful in patients with severe MR. Lately, edge-to-edge repair has also emerged as a possible treatment for severe TR in patients at high risk for cardiac surgery. In patients with both severe MR and TR, the yield of concomitant transcatheter mitral and tricuspid valve repair (TMTVR) for patients at high surgical risk is unknown. The characteristics, procedural data, and 1-year outcomes of all patients in the international multicenter TriValve registry and the German multicenter TRAMI registry, who presented with both severe MR and TR, were retrospectively compared. Patients in TRAMI (n = 106) underwent isolated TMVR, while those in TriValve (n = 122) additionally underwent concurrent TMTVR in compassionate and/or off-label use. All 228 patients (mean age 77 ± 8 years, 44.3% women) presented with significant dyspnea at baseline (New York Heart Association functional class III or IV in 93.9%), without any differences in the rates of pulmonary hypertension and chronic pulmonary disease. The proportion of patients with left ventricular ejection fraction <30% was higher in the TMVR group (34.9% vs. 18.0%; p < 0.001), while patients in the TMTVR group had lower glomerular filtration rates. At discharge, MR was comparably reduced in both groups. At 1 year, overall all-cause mortality was 34.0% in the TMVR group and 16.4% in the TMTVR group (p = 0.035, Cox regression). On multivariate analysis, TMTVR was associated with a 2-fold lower mortality rate (hazard ratio: 0.52; p = 0.02). The rate of patients in New York Heart Association functional class ≤II at 1 year did not differ (69.4% vs. 67.0%; p = 0.54). Concurrent TMTVR was associated with a higher 1-year survival rate compared with isolated TMVR in patients with both MR and TR. Further randomized trials are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to describe the impact of frailty in patients undergoing percutaneous mitral valve repair (PMVR). Background Frailty is common in elderly patients and those with comorbidities and is associated with adverse prognosis. Methods Frailty according to the Fried criteria was assessed in consecutive patients admitted for PMVR. Associations of frailty with 6-week (device success, changes in 6-min walking distance and Minnesota Living With Heart Failure Questionnaire and Short Form 36 physical and mental component scores, and improvement ≥1 New York Heart Association functional class) and long-term outcomes during a median follow-up period of 429 days were examined. Results Of 213 patients admitted for PMVR (median age 78 years; age range 50 to 95 years; 57.3% men), 45.5% were classified as frail. Compared with nonfrail patients, frail patients had a similar device success rate (81.4% vs. 84.5%; p = 0.56) and improvement in 6-min walking distance, New York Heart Association functional class, and Short Form-36 scores but a more pronounced improvement in Minnesota Living With Heart Failure Questionnaire score (mean change −15.9 vs. −11.2 points; p = 0.002). Mortality at 6 weeks was significantly higher in frail (8.3%) compared with nonfrail (1.7%) patients (p = 0.03). Hazards of death (hazard ratio: 3.06; 95% confidence interval: 1.54 to 6.07; p = 0.001) and death or heart failure decompensation (hazard ratio: 2.03; 95% confidence interval: 1.22 to 3.39; p = 0.007) were significantly increased in frail patients during long-term follow-up, which did not change relevantly after adjustment for European System for Cardiac Operative Risk Evaluation score and N-terminal pro–brain natriuretic peptide level. Conclusions PMVR can be performed with equal efficacy and is associated with at least similar short-term functional improvement in frail patients. These results support the continued use of PMVR in frail elderly patients with the goal of palliation of heart failure symptoms and improvement in quality of life. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to identify predictors of permanent pacemaker implantation (PPMI) following transcatheter aortic valve replacement (TAVR) with a balloon-expandable transcatheter valve (Edwards SAPIEN 3). Background New-onset conduction disturbances requiring PPMI remain a major concern following TAVR. Predictors are not yet well defined. Methods The influence of angiographic implantation depth, device landing zone calcium volume, oversizing, pre- and post-dilation, and baseline conduction disturbances on PPMI rate was analyzed in 229 patients undergoing TAVR with the SAPIEN 3 device. Results PPMI was performed in 14.4% of patients. Patients requiring PPMI had higher left ventricular outflow tract (LVOT) calcium volume in the area below the left coronary cusp (LVOT LC ) and the area below right coronary cusp (LVOT RC ) (LVOT LC median calcium 23.7 mm 3 vs. 3.0 mm 3 ; p < 0.001; LVOT RC median calcium 6.6 mm 3 vs. 0.3 mm 3 ; p = 0.014), a higher prevalence of pre-existing right bundle branch block (15% vs. 2%, p = 0.004), and lower implantation depth (ventricular portion of the stent frame 29 ± 12% vs. 21 ± 5%; p < 0.001). On multivariate regression analysis, LVOT LC calcium volume >13.7 mm 3 , LVOT RC calcium volume >4.8 mm 3 , pre-existing right bundle branch block, and implantation depth >25.5% emerged as independent predictors of PPMI. Upon modification of the implantation technique, aiming at a high final valve position, implantation depth decreased from 24% ventricular portion to 21% (p = 0.012), accompanied by a decrease in PPMI rate (19.2% vs. 9.2%; p = 0.038). Conclusions LVOT LC and LVOT RC calcium load, baseline right bundle branch block, and implantation depth were identified as independent predictors of the need for PPMI post-TAVR. Patient groups with different PPMI risk could be stratified using these 4 predictors. A slightly higher valve implantation site may prevent excessive PPMI rates. [ABSTRACT FROM AUTHOR]

Objectives This study sought to show safety and efficacy of the Cardioband system during 6 months after treatment. Background Current surgical and medical treatment options for functional mitral regurgitation (FMR) are limited. The Cardioband system (Valtech Cardio, OrYehuda, Israel) is a novel transvenous, transseptal direct annuloplasty device. Methods Thirty-one patients (71.8 ± 6.9 years of age; 83.9% male; EuroSCORE II: 8.6 ± 5.9) with moderate to severe FMR, symptomatic heart failure, and depressed left ventricular function (left ventricular ejection fraction 34 ± 11%) were prospectively enrolled. Results Procedural success rate, defined as delivery of the entire device, was 100%. There were no periprocedural deaths (0%), and mortality rate at 1 month or prior to hospital discharge and at 7 months was 5% and 9.7% respectively. Cinching of the implanted Cardioband reduced the annular septolateral dimension by >30% from 3.7 ± 0.5 cm at baseline to 2.5 ± 0.4 cm after 1 month and to 2.4 ± 0.4 cm after 6 months, respectively (p < 0.001). Percentage of patients with FMR ≥3 was reduced from 77.4% to 10.7% 1 month after the procedure (p < 0.001) and 13.6% (p < 0.001) at 7 months. Percentage of patients with New York Heart Association functional class III/IV decreased from 95.5% to 18.2% after 7 months (p < 0.001); exercise capacity as assessed by 6-min walking test increased from 250 ± 107 m to 332 ± 118 m (p < 0.001) and quality of life (Minnesota Living With Heart Failure Questionnaire) was also significantly improved (p < 0.001). Conclusions In this feasibility trial in symptomatic patients with FMR, transcatheter mitral annuloplasty with the Cardioband was effective in reducing MR and was associated with improvement in heart failure symptoms and demonstrated a favorable safety profile. (Cardioband With Transfemoral Delivery System; NCT01841554 ) [ABSTRACT FROM AUTHOR]

Objective Perioperative complications in patients undergoing transcatheter aortic valve implantation remain a major issue affecting outcome. Because preoperative risk adjustment remains challenging and a valid scoring system is missing, we sought to determine the incidence of peri- and postprocedural complications of transapical (TA) or transaortic (TAO) access to define the influence of specific complications on early safety, 30-day mortality, and 1-year survival. Furthermore, we aimed to develop a risk-stratification model to allow an estimation of the perioperative risk and the 1-year survival rate, based on the individual preoperative condition of each patient. Methods We performed an outcome analysis of 230 consecutive patients who underwent aortic valve implantation via transapical or transaortic access between 2008 and 2012, with regard to Valve Academic Research Consortium II criteria, including univariate and multivariable regression analysis, to develop a risk-stratification model. Results Thirty-day mortality was 12.7%. Estimated 1-year survival was 0.69 (95% confidence interval [CI], 0.631-0.757), and 3-year survival was 0.554 (95% CI, 0.474-0.634). Univariate logistic regression analysis revealed a significant influence on 30-day mortality in case of life-threatening bleeding (16.1-fold), abdominal complications (8.5-fold), and acute kidney injury (3.2-fold). Pacemaker implantation (odds ratio, 1.55; 95% CI, 0.42-5.81; P = .512) was not a significant predictor. Concerning use of intraprocedural hemodynamic bridging therapy via cardiopulmonary bypass (CPB), Cox regression analysis revealed no significant survival difference after 1 year. A preoperative risk-stratification model for 1-year survival revealed that a logistic European System for Cardiac Operative Risk Evaluation score >20%, preoperative existing coronary artery disease, and prior myocardial infarction appeared to be significant predictors for diminished survival. Conclusions Concerning intraprocedural complications, CPB support for hemodynamic stabilization is a safe treatment option. Therefore, the heart team approach with CPB standby represents a life-saving option. Attention should also be drawn to specialized and individual postoperative care, because nonprocedure-specific complications clearly affect postoperative short- and long-term outcome. In addition, the risk-stratification model might facilitate preoperative decision making. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to assess predictors of acute procedural failure in surgical high-risk patients undergoing MitraClip (Abbott Vascular, Abbott Park, Illinois) therapy. Background: MitraClip implantation is a novel percutaneous option to treat significant mitral regurgitation (MR). Methods: In 300 patients (75 ± 9 years of age, 190 [63%] men), of whom 32 (10.7%) had been unsuccessfully treated (discharge MR grade of >2+), baseline clinical and echocardiographic variables were evaluated by exact logistic regression and classification tree analyses to assess their impact on acute procedural failure. Acute procedural failure was differentiated into aborted procedure (no MitraClip implanted; n = 11) and “clip failure” (inadequate MR reduction despite MitraClip implantation; n = 21). Results: Multivariate logistic regression identified effective regurgitant orifice area (EROA), mitral valve orifice area (MVOA), and mean transmitral pressure gradient (TMPG) as independent predictors of overall acute procedural failure. Classification tree analysis revealed that an EROA >70.8 mm2 (n = 28) was associated with a high rate (25%) of clip failures, whereas the combination of an MVOA ≤3.0 cm2 and a TMPG ≥4 mm Hg (n = 16) was associated with a high rate (37.5%) of aborted procedures. Failure rates of ≤10% were observed in all patients with an EROA ≤70.8 mm2 and either an MVOA >3.0 cm2 (n = 217) or an MVOA ≤3.0 cm2 in concert with a TMPG ≤3 mm Hg (n = 39). Multinomial logistic regression identified an EROA >70.8 mm2 and a TMPG ≥4 mm Hg as independently predictive of clip failure, but an MVOA ≤3.0 cm2 and a TMPG ≥4 mm Hg as independently predictive of procedure abortion. Conclusions: In surgical high-risk patients undergoing MitraClip therapy, a TMPG ≥4 mm Hg, an EROA ≥70.8 mm2, and an MVOA ≤3.0 cm2 carry an increased risk of procedural failure. [Copyright &y& Elsevier]

Introduction: Head and neck squamous cell carcinomas (HNSSCs) are one of the leading causes of cancer-associated death worldwide. Although certain behavioral risk factors are well recognized as tumor promoting, there is very little known about the presence of predisposing germline mutations in HNSCC patients.Methods: In this study, we analyzed 121 individuals with HNSCCs collected at our institution for germline alterations in the newly identified cancer susceptibility gene RAD51C.Results: Sequencing of all exons and the adjacent introns revealed five distinct heterozygous sequence deviations in RAD51C in seven patients (5.8%). A female patient without any other risk factors carried a germline mutation that disrupted the canonical splice acceptor site of exon 5 (c.706-2A>G).Conclusions: As there are only a few publications in the literature identifying germline mutations in head and neck cancer patients, our results provide the first indication that paralogs of RAD51, recently described as mutated in breast and ovarian cancer patients, might also be candidates for genetic risk factors in sporadic squamous cell carcinomas of the head and neck. [ABSTRACT FROM AUTHOR]

Background: Optimal transcatheter aortic valve (TAVI) results require accurate valve positioning, including anatomically correct orientation and secure fixation within the aortic annulus, thereby potentially decreasing paravalvular regurgitation. The new Engager (Medtronic 3F Therapeutics, Santa Ana, CA) transapical valve system captures the native leaflets for sealing and allows for tactile feedback during valve placement. We report initial safety and performance outcomes of the Engager system through 6 months in patients with severe aortic valve stenosis at high risk for surgical aortic valve replacement. Methods: An interim analysis was performed on the first 61 enrolled September 2011 through May 2012. Inclusion criteria comprised severe aortic stenosis, New York Heart Association functional class of II or greater, logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) of 20% or greater, or contraindication to surgical aortic valve replacement. The primary endpoint was all-cause mortality at 30 days. Patients were evaluated 24 to 48 hours post-procedure, at hospital discharge, 30 days and 6 months. Follow-up is planned annually through five years. Results: Baseline characteristics for the 61 patients were mean age 81.9 ± 4.4 years, 62.3% female, 88.5% New York Heart Association class III/IV, 52.5% coronary artery disease, and 54.2% extracardiac arteriopathy. For all of the attempted implantations (n = 60), the Engager prosthesis was positioned in the correct anatomic position without conversions to surgery, second valve implantation, device malposition, aortic annular rupture, or coronary obstruction. All-cause mortality was 9.9% at 30 days and 16.9% at 6 months. The baseline mean aortic valve gradient was 43.7 ± 16.7 mm Hg and 11.5 ± 5.0 mm Hg at 30 days, and showed similar reduction at 6 months (13.9 ± 6.2 mm Hg). There was no paravalvular regurgitation greater than mild through 6 months. Conclusions: Early postoperative results support implantation success and valve safety. Analysis for 6 month outcomes shows stable hemodynamic performance and clinical outcome. (Transapical Implantation of the Medtronic Engager Transcatheter Aortic Valve Implantation System—the Engager European Pivotal Trial; NCT01348438) [Copyright &y& Elsevier]

Objectives: This study sought to report on the feasibility and early results of transcatheter aortic valve implantation employing a second-generation device in a series of patients with pure aortic regurgitation. Background: Efficacy and safety of transcatheter aortic valve implantation in patients with calcific aortic stenosis and high surgical risk has been demonstrated. However, experience with implantation for severe noncalcified aortic regurgitation has been limited due to increased risk for valve dislocation or annular rupture. Methods: Five patients (mean age: 66.6 ± 7 years) underwent transapical implantation of a JenaValve (JenaValve Technology GmbH, Munich, Germany) transcatheter heart valve for moderate to severe, noncalcified aortic regurgitation. All patients were considered high risk for surgical aortic valve replacement after evaluation by an interdisciplinary heart team (logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation] range 3.1% to 38.9%). Procedural and acute clinical outcomes were analyzed. Results: Implantation was successful in all cases without relevant remaining aortic regurgitation or signs of stenosis in any of the patients. No major device- or procedure-related adverse events occurred and all 5 patients were alive with improved exercise tolerance at 3-month follow-up. Conclusions: Noncalcified aortic regurgitation continues to be a challenging pathology for transcatheter aortic valve implantation due to the risk for insufficient anchoring of the valve stent within the aortic annulus. This report provides first evidence that the JenaValve prosthesis may be a reasonable option in these specific patients due to its unique stent design, clipping the native aortic valve leaflets, and offering promising early results. [Copyright &y& Elsevier]

Objectives: This study reports the results of a series of transapical mitral valve-in-valve implantations and aims to offer guidance on technical aspects of the procedure. Background: Mitral valve reoperations due to failing bioprostheses are associated with high morbidity and mortality. Transcatheter techniques may evolve as complementary approaches to surgery in these high-risk patients. Methods: Six patients (age 75 ± 15 years) received transapical implantation of a balloon-expandable pericardial heart valve into a degenerated bioprosthesis (range 27 to 31 mm) in mitral position at our institution. All patients were considered high risk for surgical valve replacement (logistic EuroSCORE: 33 ± 15%) after evaluation by an interdisciplinary heart team. Procedural and clinical outcomes were analyzed. Results: Implantation was successful in all patients with reduction of mean transvalvular gradients from 11.3 ± 5.2 mm Hg to 5.5 ± 3.6 mm Hg (p = 0.016) and median regurgitation from grade 3.0 (interquartile range [IQR]: 2.7 to 3.1) to 0 (IQR: 0 to 1.0, p = 0.033) with trace paravalvular regurgitation remaining in 2 patients. Apical bleeding occurred in 2 patients requiring rethoracotomy in 1 and resuscitation in a second patient, the latter of whom died on postoperative day 6. In the remaining patients, median New York Heart Association functional class improved from 3.0 (IQR: 3.0 to 3.5) to 2.0 (IQR: 1.5 to 2.0, p = 0.048) over a median follow-up of 70 (IQR: 25.5 to 358) days. Conclusions: With acceptable results in a high-risk population, transapical mitral valve-in-valve implantation can be considered as a complementary approach to reoperative mitral valve surgery in select patients. [ABSTRACT FROM AUTHOR]

Objective: Transcatheter valve-in-valve implantation is evolving as an alternative to reoperative valve replacement in high-risk patients with degenerated bioprostheses. Nevertheless, hemodynamic performance is limited by the previously implanted xenograft. We report our experience with patient–prosthesis mismatch (PPM) after valve-in-valve implantation in the aortic position. Methods: Eleven patients (aged 79.3 ± 6.1 years) received transapical implantation of a balloon-expandable pericardial heart valve into a degenerated bioprosthesis (size, 23.9 ± 1.6 mm; range, 21–27 mm) in the aortic position. All patients were considered high risk for surgical valve replacement (logistic European System for Cardiac Operative Risk Evaluation, 31.8% ± 24.1%). Severe PPM was defined as an indexed effective orifice area less than 0.65 cm2/m2, determined by discharge echocardiography. Results: Severe PPM was evident in 5 patients (group 1) and absent in 6 patients (group 2). Mean transvalvular gradients decreased from 29.2 ± 15.4 mm Hg before implantation to 21.2 ± 9.7 mm Hg at discharge (group 1) and from 28.2 ± 9.0 mm Hg before implantation to 15.2 ± 6.5 mm Hg at discharge (group 2). Indexed effective orifice area increased from 0.5 ± 0.1 cm2/m2 to 0.6 ± 0.1 cm2/m2 and from 0.6 ± 0.3 cm2/m2 to 0.8 ± 0.3 cm2/m2. Aortic regurgitation decreased from grade 2.0 ± 1.1 to 0.4 ± 0.5 overall. No differences in New York Heart Association class improvement or survival during follow-up were observed. One patient required reoperation for symptomatic PPM 426 days after implantation. Conclusions: Valve-in-valve implantation can be performed in high-risk surgical patients to avoid reoperation. However, PPM frequently occurs, making adequate patient selection crucial. Small bioprostheses (<23 mm) should be avoided. Implantation into 23-mm xenografts can be recommended only for patients with a body surface area less than 1.8 m2. Larger prostheses seem to carry a lower risk for PPM. Although no delay in clinical improvement was seen at short-term, 1 PPM-related surgical intervention raises concern regarding long-term performance. [Copyright &y& Elsevier]

Objective: Surgical mitral valve repair carries an elevated perioperative risk in the presence of severely reduced ventricular function and relevant comorbidities. We sought to assess the feasibility of catheter-based mitral valve repair using a clip-based percutaneous edge-to-edge repair system in selected patients at high surgical risk with mitral regurgitation grade 3 or worse. Methods: Between 2002 and January 2011, 202 consecutive patients without prior mitral valve surgery (age 75 ± 9 years; 63% were male) with symptomatic functional (65%), degenerative (27%), or mixed (8%) mitral regurgitation were treated with a percutaneous clip system for approximation of the anterior and posterior mitral leaflets. Risk for mitral valve surgery was considered high in terms of a mean logistic European System for Cardiac Operative Risk Evaluation of 44% (range, 21%–54%). Preprocedural left ventricular ejection fraction was 35% or less in 36% of patients. An interdisciplinary heart team of cardiologists and cardiac surgeons discussed all patients. Results: Percutaneous clip implantation was successful in 186 patients (92%). Patients were treated with 1 clip (n = 125; 62%), 2 clips (n = 64; 32%), or 3 or more clips (n = 7; 3%). Reduction in mitral regurgitation from pre- to postprocedure was significant (P < .0001) and remained stable within the first 12 months in the majority of patients. Thirty-day mortality was 3.5% (7/202 patients). Hospital stay was 12 ± 10 days, and median intensive care unit stay was 1 day (range, 0–45 days). Eleven patients required surgical valve repair/replacement at a median of 38 days (0–468 days) after percutaneous clip implantation. Conclusions: Clip-based percutaneous mitral valve repair is a safe, low-risk, and effective therapeutic option in symptomatic patients with a high risk for surgery and does not exclude later surgical repair. [Copyright &y& Elsevier]

Objectives: Transcatheter aortic valve implantation (TAVI) has recently been advocated to decrease perioperative risk in high-risk patients. In this propensity-score analysis we compared outcomes after TAVI to those after surgical aortic valve replacement (AVR). Methods: From June 2009 through June 2010, 82 consecutive patients underwent TAVI via a transapical (n = 60) or transfemoral (n = 22) approach using the Edwards Sapien prosthesis (Edwards Lifesciences, Irvine, Calif). Mean patient age was 81.9 ± 5.2 years, 64.6% were women. Logistic EuroSCORE was 23.6% ± 1.4% and Society of Thoracic Surgeons score was 8.7% ± 1.3%. A group of 82 patients after surgical AVR was retrieved from our database, yielding a control group that was matched to the cases with respect to baseline demographics and typical risk factors. Results: Overall mortality did not differ significantly between TAVI and AVR groups at 30 days (7.3% vs 8.6%), 90 days (13.6% vs 11.1%), or 180 days (17.8% vs 16.9%; P = .889). Conversion to surgery was necessary in 2 (2.4%) TAVI cases. Perioperative stroke occurred in 2 (2.4%) cases per group. Pacemakers were implanted for new-onset heart block in 3.7% and 2.4% in the TAVI and AVR groups, respectively (P = 1.0). TAVI resulted in shorter operative times (P < .001), shorter ventilation times (P < .001), and shorter length of stay in the intensive care unit (P = .008). Duration of hospital stay, however, was not significantly different (P = .11). Conclusions: In our experience, mortality rates are similar after both types of procedure. Patients receiving TAVI benefit from faster postoperative recovery. Until more clinical data become available, the optimal procedure has to be determined for each patient according to individual risk factors. [Copyright &y& Elsevier]

Background: Along with primary tumor response, lymph node (LN) status after radiochemotherapy is one of the most important prognostic factors for advanced esophageal carcinoma. We investigated the influence of neoadjuvant radiochemotherapy on histomorphologic parameters of LNs. Methods: One hundred ninety-two patients with esophageal carcinoma underwent surgery after preoperative radiochemotherapy. Response of primary tumor was graded as “minor” or “major.” Two matched subgroups were chosen: 20 patients with minor response and 20 patients with major response. Histomorphologic criteria of LNs underwent univariate and multivariate analyses and correlated with tumor response and prognosis statistics. Results: The LNs from 40 patients (N = 1276) were examined (median number of LNs per patient, 31). Of patients with minor response, 65% showed LN metastasis; of those with major response, 20% did so (p = 0.011). Major responders had significantly lower rates of capsular and central fibrosis and vascular transformation and had more sarcoidlike lesions. Logistic regression analysis did not distinguish these parameters between major and minor responders. The 5-year survival rate was 55% for major responders and 10% for minor responders (p = 0.025), 47% for patients with LN metastasis (LNM) and 18% for patients with LNM (p = 0.041). An optimal prognostic factor, LN morphologic grading, was defined as follows: low risk, no LNM and less than 3 LNs with central fibrosis; medium risk, no LNM and central fibrosis in 3 or more LNs or LNM with an LN ratio of less than 0.05; high risk, all other cases. The 5-year survival rate was 56%, 25%, and 0% for patients considered to have low, medium, and high risk, respectively, according to LN morphologic grading (p < 0.003). With the inclusion of this classification in the Cox regression analysis, no other factors showed prognostic relevance. Conclusions: Grading of LN morphology after neoadjuvant radiochemotherapy is the most important prognostic factor for patients with esophageal cancer. [Copyright &y& Elsevier]

Background: Pancreatic cancer still has one of the worst prognoses of all cancers with a 5-year survival rate of 5%, making it necessary to find markers or gene sets that would further classify patients into different risk categories and thus allow more individually adapted multimodality treatment regimens. Especially heparanase (HPSE) has recently been discussed as a key factor in pancreatic cancer.Materials and Methods: Paraffin-embedded tissue samples were obtained from 41 patients with pancreatic adenocarcinoma who were scheduled for primary surgical resection. Direct quantitative real-time reverse transcriptase polymerase chain reaction (TaqMan) assays were performed in triplicates to determine HPSE, hypoxia inducible factor-1 alpha (HIF1a), platelet-derived growth factor alpha (PDGFA), heparin-binding EGF-like growth factor (HB-EGF), and basic fibroblast growth factor (bFGF) gene expression levels.Results: HPSE was significantly correlated to PDGFA (p = 0.04) and HIF1a (p = 0.04). The correlation of HIF1a to bFGF and HB-EGF was significant (p = 0.04, p = 0.02). Stepwise multiple linear regression models showed a significant independent association of HPSE with lymph node metastasis (p = 0.025) and with dedifferentiation (p = 0.042).Conclusions: Heparanase seems to be significantly associated with lymph node metastasis (p = 0.025) as well as dedifferentiation (p = 0.042). We assume that HPSE plays a crucial role for the aggressiveness of pancreatic cancer. Larger studies including more patients seem to be warranted. [ABSTRACT FROM AUTHOR]

Background: Little is known about the role of cyclooxygenase (COX)-2 in gastroesophageal reflux disease (GERD) and the development of Barrett's metaplasia. The objectives of this study were to further analyze COX-2 mRNA expression in patients with GERD compared to Barrett's esophagus (BE) and Barrett's cancer (BC).Methods: Tissue samples from 110 patients with GERD (n = 43), BE (n = 20), and BC (n = 47) were obtained in routine upper GI endoscopy. Expression levels of COX-2 were measured by quantitative real-time reverse trancriptase polymerase chain reaction (RT-PCR). Also, 24-h pH monitoring was performed in all patients of the GERD study group and the DeMeester composite score was used to match COX-2 mRNA expression with the severity of acid exposure in the lower esophagus.Results: COX-2 mRNA is progressively upregulated within the metaplasia-dysplasia-adenocarcinoma (MDA) sequence (p = 0.001). COX-2 levels of the squamous epithelium in the distal esophagus from patients with GERD and a pathologic mean DeMeester score (>14.72) were significantly higher than in patients with normal DeMeester scores (p = 0.01).Conclusion: In summary our findings suggest that alterations in COX-2 mRNA expression occur independently of endoscopic or histologic signs of GERD in the acid-exposed squamous epithelium of the distal esophagus. However, this early COX-2 increase in GERD is further upregulated within the MDA sequence for yet unknown reasons. [ABSTRACT FROM AUTHOR]

Abstract: Reactive oxygen species, in particular superoxide, have been closely linked to the underlying pathophysiology of ischemic cardiomyopathy: superoxide not only mediates mechanoenergetic uncoupling of the myocyte but also adversely impacts on myocardial perfusion by depleting endothelial-derived nitric oxide bioavailability. Xanthine oxidase generates superoxide upon oxidation of hypoxanthine and xanthine and has been detected in cardiac myocytes and coronary endothelial cells of patients with ischemic heart disease. Here we investigated the effects of oxypurinol, a xanthine oxidase inhibitor, on myocardial contractility in patients with ischemic cardiomyopathy. Twenty patients (19 males, 66±8 years) with stable coronary disease, severely suppressed systolic function (left ventricular ejection fraction 22±2%), and nonelevated uric acid plasma levels received a single intravenous dose of oxypurinol (400 mg). Cardiac MRI studies, performed before and 5.2±0.9 h after oxypurinol administration, revealed a reduction in end-systolic volumes (−9.7±4.2%; p =0.03) and an increase in left ventricular ejection fraction (+17.5±5.2%; p =0.003), whereas 6 patients (6 males, 63±3.8 years, ejection fraction 26±5%) who received vehicle only did not show significant changes in any of the parameters studied. Oxypurinol improves left ventricular function in patients with ischemic cardiomyopathy. These results underscore the significance of reactive oxygen species as important pathophysiological mediators in ischemic heart failure and point toward xanthine oxidase as an important source of reactive species that serve to modulate the myocardial redox state in this disease. [Copyright &y& Elsevier]

Abstract: Myeloperoxidase (MPO), a heme protein abundantly expressed in polymorphonuclear neutrophils (PMN), has long been viewed to function primarily as a bactericidal enzyme centrally linked to innate host defense. Recent observations now extend this perspective and suggest that MPO is profoundly involved in the regulation of cellular homeostasis and may play a central role in initiation and propagation of acute and chronic vascular inflammatory disease. For example, low levels of MPO-derived hypochlorous acid (HOCl) interfere with intracellular signaling events, MPO-dependent oxidation of lipoproteins modulates their affinity to macrophages and the vessel wall, MPO-mediated depletion of endothelial-derived nitric oxide (NO) impairs endothelium-dependent vasodilatation, and nitrotyrosine (NO2Tyr) formation by MPO sequestered into the vessel wall may affect matrix protein structure and function. Future studies are needed to further elucidate the significance of MPO in the development of acute and chronic vascular disease and to evaluate MPO as a potential target for treatment. [Copyright &y& Elsevier]