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In the early 1990s, the idea of Transcatheter Aortic Valve Implantation (TAVI) emerged from clinicians by the insight that the long-term hemodynamic and clinical results of aortic balloon valvuloplasty to treat aortic stenonosis were not satisfying. Thus, Anderson and Cribier developed the balloon-expandable and Figulla and Laborde the self-expendable TAVI systems. Sceptical views by the surgical colleagues and the industry delayed the rapid development of this disruptive new therapy until 2002, when Alain Cribier demonstrated for the first time the proof of his concept. Bulky devices and paravalvular leakages in patients treated in terms of compassionate care resulted in high mortality rates. From 2005 onwards, the treatment of patients not at highest risk using smoother devices in clinical trials could demonstrate that the technology was equivalent to surgical aortic valve replacement. The transapical access route initiated the heart team approach with the surgical colleagues, however, this access route is presently expiring due to its greater trauma. The need to treat also aortic regurgitation is addressed by the "clipping technology" of JenaValve™. Ongoing clinical trials investigate an extended indication for TAVI at an earlier stage of aortic stenosis, or in reduced ejection fraction, and just demonstrated the safety and efficiency even in low surgical risk patients.

Transcathetertherapy has expanded the treatment options for patients with heart valve disease. Interventional therapy for aortic, mitral, and pulmonic valve disease is well established; however, catheter-based approaches to tricuspid regurgitation (TR) are still in early stages of development. For some of the interventional concepts to TR, including the edge-to-edge-repair, transcatheter annuloplasty, the tricuspid spacer, and caval valves, procedural feasibility and favorable early clinical outcome have been demonstrated in small compassionate case series. This article reviews the pathophysiological background and current evidence for caval valve implantation and examines the potential role of this approach for the treatment of severe TR.

Objectives The authors investigated the development of pulmonary hypertension (PH), predictors of PH regression, and its prognostic impact on short, mid-, and long-term outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS). Background PH represents a common finding in patients with AS. Although TAVR is frequently associated with regression of PH, the predictors of reversible PH and its prognostic significance remain uncertain. Methods In this study, 617 consecutive patients undergoing TAVR between 2009 and 2015 were stratified per baseline tertiles of pulmonary artery systolic pressure (PASP) as follows: normal (PASP Results In patients with both mild-to-moderate and severe PH at baseline, PASP decreased significantly at discharge (ΔPASP 3.0 ± 9.3 mm Hg and 12.0 ± 10.0 mm Hg, respectively) and 1 year (ΔPASP 5.0 ± 9.7 mm Hg and 18.0 ± 14.0 mm Hg, respectively). At a median follow-up of 370 days (interquartile range [IQR]: 84 to 500 days), the risk of all-cause mortality was similar among baseline PASP groups at all time intervals evaluated. After TAVR, a significant regression of PH was observed in 46% of patients. Contrarily, patients with residual PH had a higher risk of all-cause mortality at 30 days (hazard ratio [HR]: 3.49, 95% confidence interval [CI]: 1.74 to 6.99; p 40% (odds ratio [OR]: 3.56, 95% CI: 2.24 to 5.65; p Conclusions In most patients with PH and AS, TAVR is associated with a significant early and late reduction of PASP. Patients with reversible PH after TAVR are at lower risk of all-cause mortality at early, mid-, and long-term follow-up. Therefore, the presence of PH should not preclude treatment with TAVR.

AIMS Evaluation of aortic stenosis (AS) is based on echocardiographic measurement of mean pressure gradient (MPG), flow velocity (Vmax) and aortic valve area (AVA). The objective of the present study was to analyse the impact of systemic haemodynamic variables and concomitant mitral regurgitation (MR) on aortic MPG, Vmax and AVA in severe AS. METHODS AND RESULTS A pulsatile circulatory model was designed to study function and interdependence of stenotic aortic (AVA: 1.0 cm², 0.8 cm² and 0.6 cm²) and insufficient mitral prosthetic valves (n=8; effective regurgitant orifice area [EROA] 0.4 cm²) using Doppler ultrasound. In the absence of severe MR, a stepwise increase of stroke volume (SV) and a decrease of AVA was associated with a proportional increase of aortic MPG. When MR with EROA 0.4 cm² was introduced, forward SV decreased significantly (70.9±1.1 ml vs. 60.8±1.6 ml vs. 47.4±1.1 ml; p=0.02) while MR volume increased proportionally. This was associated with a subsequent reduction of aortic MPG (57.1±9.4 mmHg vs. 48.6±13.8 mmHg vs. 33.64±9.5 mmHg; p=0.035) and Vmax (5.09±0.4 m/s vs. 4.91±0.73 m/s vs. 3.75±0.57 m/s; p=0.007). Calculated AVA remained unchanged (without MR: AVA=0.53±0.04 cm² vs. with MR: AVA=0.52±0.05 cm²; p=ns). In the setting of severe AS without MR, changes of vascular resistance (SVR) and compliance (C) did not impact on aortic MPG (low SVR and C: 66±13.8 mmHg and 61.1±20 mmHg vs. high SVR and C: 60.9±9.2 mmHg and 71.5±13.5 mmHg; p=ns) In concomitant severe MR, aortic MPG and Vmax were not significantly reduced by increased SVR (36.6±2.2 mmHg vs. 34.9±5.6 mmHg, p=0.608; 3.89±0.18 m/s vs. 3.96±0.28 m/s; p=ns). CONCLUSIONS Systemic haemodynamic variables and concomitant MR may potentially affect diagnostic accuracy of echocardiographic AS evaluation. As demonstrated in the present study, MPG and Vmax are flow-dependent and significantly reduced by a reduction of forward SV from concomitant severe MR, resulting in another entity of low-flow low-gradient aortic stenosis. In contrast, calculated AVA appears to be a robust parameter of AS evaluation if severe MR is present. Changes of SVR and C did not affect the diagnostic accuracy of AS evaluation.

Recently, transcatheter therapy has expanded the treatment options for patients with heart valve disease. With the growing understanding of tricuspid regurgitation and its natural history, it becomes increasingly obvious that this patient population is a heterogeneous cohort presenting for treatment in different stages of a continuous disease process. It is still unclear which interventional approach will result in functional and clinical success and in which subtype of patient population. This article reviews the pathophysiologic background and current evidence for caval valve implantation and examines the potential role of this approach for the treatment of severe tricuspid regurgitation.

BACKGROUND Endothelial dysfunction is accompanied by the release of microparticles (MP). OBJECTIVE We sought to investigate the effect of moderate hypoxia on circulatory levels of microparticles, biomarkers of cardiovascular function and inflammation and on echocardiographic parameters in healthy volunteers staying at an altitude of 2978 m. METHODS Eighteen healthy volunteers were subjected to moderate hypoxia by staying at 2978 m above sea level for three days. Blood samples were evaluated for MP using flow cytometry. ELISA analysis was performed for sST2, H-FABP, suPAR and GDF-15. Moreover, the effect of dual endothelin-receptor blockade was investigated. RESULTS Oxygen saturation decreased to 93%. A significant decrease of endothelial and platelet MP levels was found. These results were corroborated by a similar response in sST2 and suPAR plasma concentration. Endothelin-receptor blockade by macitentan only had a marginal influence on MP, sST2, H-FABP, suPAR and GDF-15 levels, though it led to a significant amelioration of echocardiographic parameters of right heart function. CONCLUSIONS These experimental results show that moderate hypoxia due to altitude exposition led to a reduction in parameters of endothelial dysfunction as shown by a decrease in endothelial and platelet MP, sST2 and suPAR levels. A slight increase in pulmonary pressure at moderate altitude was decreased by dual endothelin receptor blockade.

Aims Vena contracta area (VCA3D), derived by 3D colour Doppler echocardiography, has already been validated against cardiac magnetic resonance imaging, but the number of clinical studies to define cut-off values for grading of mitral regurgitation (MR) is limited. Aim of the study was to assess VCA3D in a large population of patients with functional (FMR) and degenerative MR (DMR). Methods and results Transoesophageal echocardiography was performed in 500 patients with MR. The following 2D parameters were assessed for grading of MR: vena contracta width, effective regurgitant orifice area (EROAPISA), and regurgitation volume (RVPISA). VCA3D and the corresponding regurgitation volume (RVVCA) were quantified using 3D colour Doppler loop and CW Doppler tracing of the regurgitant jet. In 104 patients a 3D dataset of the left ventricle (LV) and the left ventricular outflow tract (LVOT) was acquired. As a reference method, regurgitation volume (RV3D) was calculated as difference between LV overall and LVOT stroke volumes. For prediction of severe MR, VCA3D yielded higher values of area under the ROC curve compared to EROAPISA (overall patient group 0.98 for VCA3D vs. 0.90 for EROAPISA, P

Objectives This study sought to analyze health-related quality-of-life (HrQoL) outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) based on data from GARY (German Aortic Valve Registry). Background Typically, patients currently referred for and treated by TAVR are elderly with a concomitant variable spectrum of multiple comorbidities, disabilities, and limited life expectancy. Beyond mortality and morbidity, the assessment of HrQoL is of paramount importance not only to guide patient-centered clinical decision-making but also to judge this new treatment modality in this high-risk patient population. Methods In 2011, 3,875 patients undergoing TAVR were included in the GARY registry. HrQoL was prospectively measured using the EuroQol 5 dimensions questionnaire self-complete version on paper at baseline and 1 year. Results Complete follow-up EuroQol 5 dimensions questionnaire evaluation was available for 2,288 patients (transvascular transcatheter aortic valve replacement [TAVR-TV]: n = 1,626 and transapical TAVR [TAVR-TA]: n = 662). In-hospital mortality was 5.9% (n = 229) and the 1-year mortality was 23% (n = 893). The baseline visual analog scale score for general health status was 52.6% for TAVR-TV and 55.8% for TAVR-TA and, in parallel to an improvement in New York Heart Association functional class, improved to 59.6% and 58.5% at 1 year, respectively (p Conclusions TAVR treatment led to improvements in HrQoL, especially in terms of mobility and usual activities. The magnitude of improvements was higher in the TAVR-TV group as compared to the TAVR-TA group. However, there was a sizable group of patients who did not derive any HrQoL benefits. Several independent pre- and post-operative factors were identified being predictive for less pronounced HrQoL benefits.

The JenaValve (JV) transcatheter aortic valve implantation (TAVI) device is the first so-called third-generation device, as it incorporates many new features, such as treatment for aortic stenosis and aortic regurgitation, as well as anatomic positioning and easy deployment precisely within the aortic annulus. Its transfemoral model is expected to launch on the European market in 2018. The development started as early as 1995, and did not find support at that time from physicians, industry, or scientific grants. The first transapical model was launched on the market in 2011 for the treatment of aortic stenosis, and the only TAVI device for the treatment of aortic regurgitation came onto the market in 2013.

In the early and mid-1990s the idea of transcatheter aortic valve implantation (TAVI) was mooted by several scientists. Anderson and Cribier developed balloon-expandable TAVI systems, and Figulla and Laborde later developed self-expandable systems, because it had become evident that aortic balloon valvuloplasty did not create durable results. Skeptical views of these systems by surgical colleagues and the industry delayed the rapid development of this disruptive new therapy until 2002, when Alain Cribier demonstrated, for the first time, the proof of his concept of TAVI. However, bulky devices and paravalvular leaks in compassionate patients resulted in high mortality rates, and from 2005 onwards clinical trials of more sophisticated devices were able to demonstrate less patient risk, showing that the TAVI technology was equivalent to surgical aortic valve replacement. The employment of the transapical access route initiated the heart team approach with surgical colleagues; however, this access route is no longer common, owing to its greater trauma compared with ?. The need to also treat aortic regurgitation is addressed by the “clipping technology” of the JenaValve, and ongoing clinical trials are investigating extended indications for TAVI at an earlier stage of aortic stenosis or in patients with a reduced ejection fraction, and the safety and efficiency of TAVI for these indications is being compared with ? in low-surgical-risk patients.

// Sylvia Otto 1 , Kristin Jaeger 1 , Frank D. Kolodgie 2 , Diana Muehlstaedt 1 , Marcus Franz 1 , Sabine Bischoff 3 , Harald Schubert 3 , Hans R. Figulla 1 , Renu Virmani 2 and Tudor C. Poerner 1 1 Department of Medicine 1, Division of Cardiology, University Hospital of Jena, Thuringia, Germany 2 Institute for Laboratory Animal Science and Animal Protection (IVuT), University Hospital of Jena, Thuringia, Germany 3 CV Path Institute Inc., Gaithersburg, MD, USA Correspondence to: Sylvia Otto, email: // Keywords : PPARg, ciglitazone, endothelium, vascular remodeling, drug-eluting stents, Pathology Section Received : July 16, 2016 Accepted : August 20, 2016 Published : August 24, 2016 Abstract Aim: Peroxisome proliferator-activated receptor-gamma (PPARg) agonists have known pleiotropic cardiovascular effects with favourable properties in vascular remodeling, and specifically in suppression of vascular smooth muscle cell proliferation. A novel vascular stent coating using the PPARg ligand ciglitazone (CCS) was investigated regarding its effects on endothelialization after 7 and 28 days. Methods: Microporous bare metal stents (BMS) were coated with ciglitazone by ultrasonic flux with a load of 255 μg ciglitazone/stent. SixteenNew Zealand white rabbits, fed a with high cholesterol diet, underwent stent implantation in both iliac arteries. Everolimus-eluting stents (EES) and BMS were comparators. Histology (CD 31 immunostaining, confocal and scanning electron microscopy, morphometry) was performed after 7 and 28 days and by OCT (optical coherence tomography) in vivo after 28 days. Results: Microscopy showed comparable results with near complete endothelialization in CCS and BMS (%CD31 above stent struts after 7 days: 67.92±36.35 vs. 84.48±23.86; p = 0.55; endothel % above stent struts: 77.22±27.9 vs. 83.89±27.91; p = 0.78). EES were less endothelialized with minimal fibrin deposition, not found in BMS and CCS (% CD 31 above struts after 28 days, BMS: 100.0±0.0 vs. EES: 95.9±3.57 vs. CCS: 100.0±0.0; p = 0.0292). OCT revealed no uncovered struts in all stents after 28 days. Conclusions: Polymer-free coating with ciglitazone, a PPARg agonist is feasible and stable over time. Our data prove unimpaired endothelial coverage of a ciglitazone-coated vascular stent system by histology and OCT. Thus, this PPARg agonist coating deserves further investigation to evaluate its potency on local neointimal suppression.

Background Percutaneous coronary interventions (PCI) with drug-coated balloons (DCB) might be a promising trade-off between balloon angioplasty and drug-eluting stents, since DCB inhibit neointimal proliferation and limit duration of dual antiplatelet therapy. We investigated the safety, feasibility, and 6-month results of fractional flow reserve (FFR)-guided use of the paclitaxel-coated SeQuent Please® balloon without stenting for elective PCI of de novo lesions. Methods and results In 46 patients (54 lesions) with stable symptomatic coronary artery disease (CAD), a FFR-guided POBA (plain old balloon angioplasty) was performed. In case of a sufficient POBA result with residual stenosis 0.8 and no severe dissection, the target lesion was finally dilated using the DCB. Quantitative coronary angiography (QCA) was performed before and after the index procedure and at 6-month follow-up (f/u) to calculate late lumen loss (LLL) and net luminal gain (NLG). Optical coherence tomography (OCT) was performed at f/u to assess vascular remodeling. DCB-only treatment was applied to 43 patients (51 lesions), while 3 patients (3 lesions) needed provisional stenting. Invasive f/u was completed in 39 patients (47 lesions). At the stenotic site, the lumen diameter showed a trend toward progressive increase at f/u (LLL: −0.13 ± 0.44 mm, n.s.; NLG: 1.10 ± 0.53 mm, p

Aim of this study was the assessment of left atrial appendage (LAA) dimensions comparing 2D- to 3D-TEE measurements in patients with nonvalvular atrial fibrillation undergoing percutaneous LAA occlusion. Patients underwent transesophageal echocardiography (TEE) before, during and 45 days after intervention. The maximal LAA orifice diameters in 2D-TEE (LODmax 2D) were obtained from multiple views. Test–retest reliability (screening vs. implantation), inter- and intra-observer variability for echocardiographic parameters were assessed by two independent examiners. Overall, 74 patients underwent percutaneous LAA occlusion. 2D-TEE significantly underestimated the maximal LAA orifice diameter compared with 3D-TEE (screening LODmax 2D 21.11 ± 2.75 mm vs. 22.52 ± 3.45 mm for LODmax 3D, p

Aims To examine the effect of renal denervation (RDN) on 24‑h ambulatory blood pressure (ABP) with a standard radiofrequency ablation catheter (RF catheter). Methods Seventy-five patients with resistant hypertension received bilateral RDN with an RF catheter (6 RF applications, 1 minute each, 8–12 watts). Seventy patients fulfilled inclusion criteria with mean systolic ABP ≥140 mmHg (mean 165/89) despite treatment with ≥3 antihypertensive drugs (mean 5.9) including a diuretic, and were further analysed for ABP changes. Follow-up at 1/3/6/12 months comprised biochemical evaluations and ABP measurement. At 6/12 months, duplex sonography of the renal arteries was additionally performed. Results At 1/3/6/12 months we observed a significant reduction in systolic ABP of −15/−17/−18/−15 mmHg (n = 55/53/57/50; non-parametric Friedman test, p 70 %) with subsequent stenting without complications. Logistic regression analysis with systolic ABP reduction ≥10 mmHg at 12 months follow-up as criterion revealed that only the mean baseline systolic ABP was significant, OR = 2.174. Conclusions RDN with a standard RF catheter can be used safely to reduce mean ABP in resistant hypertension as shown in long-term follow-up.

Background Conventional aortic valve replacement (AVR) remains the therapy of choice for many patients with severe aortic valve disease. The unique German Aortic Valve Registry (GARY) allows the comparison of contemporary outcomes of AVR with those of transcatheter AVRs. We report here real-world, all-comers outcomes of AVR, including combined AVR and coronary bypass grafting (AVR+CABG). Methods A total of 34,063 patients who received AVR (22,107 patients, 39% female; mean age 68.0 ± 11.3 years, mean logistic European System for Cardiac Operative Risk Evaluation, 8.6%) or AVR+CABG (11,956 patients, 28% female; mean age 72.6 ± 7.8 years, mean logistic European System for Cardiac Operative Risk Evaluation, 10.7%) between 2011 and 2013 were analyzed and followed up to assess the 1-year outcome. Results In-hospital mortality was 2.3% for AVR and 4.1% for AVR+CABG. Other important outcome variables include stroke (AVR, 1.2%; AVR+CABG, 1.9%) and new pacemaker implantation (AVR, 4.4%; AVR+CABG, 3.6%). Survival at 1 year was 93.2% for AVR and 89.4% for AVR+CABG. Total stroke rates at 1 year were 1.6% for AVR and 2.0% AVR+CABG. Quality of life assessment indicated that most patients were in New York Heart Association Functional Classification I or II (AVR, 86%; AVR+CABG, 84%) and that they were satisfied with the overall postoperative course (AVR, 88%; AVR+CABG, 87%). Conclusions Contemporary surgical AVR yields excellent outcomes with low in-hospital mortality, a low overall complication rate, and good 1-year outcome for all risk groups. Accordingly, conventional AVR remains an important therapeutic option for many patients.

The authors investigated the development of pulmonary hypertension (PH), predictors of PH regression, and its prognostic impact on short, mid-, and long-term outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS).PH represents a common finding in patients with AS. Although TAVR is frequently associated with regression of PH, the predictors of reversible PH and its prognostic significance remain uncertain.In this study, 617 consecutive patients undergoing TAVR between 2009 and 2015 were stratified per baseline tertiles of pulmonary artery systolic pressure (PASP) as follows: normal (PASP 34 mm Hg), mild-to-moderate (PASP ≥34 mm Hg and 46 mm Hg), and severe PASP elevation (PASP ≥46 mm Hg). After TAVR, 520 patients with PH at discharge were stratified according to the presence or absence of PASP reduction. Primary outcome was all-cause mortality at 30 days, 1 year, and long-term follow-up at a maximum of 5.9 years.In patients with both mild-to-moderate and severe PH at baseline, PASP decreased significantly at discharge (ΔPASP 3.0 ± 9.3 mm Hg and 12.0 ± 10.0 mm Hg, respectively) and 1 year (ΔPASP 5.0 ± 9.7 mm Hg and 18.0 ± 14.0 mm Hg, respectively). At a median follow-up of 370 days (interquartile range [IQR]: 84 to 500 days), the risk of all-cause mortality was similar among baseline PASP groups at all time intervals evaluated. After TAVR, a significant regression of PH was observed in 46% of patients. Contrarily, patients with residual PH had a higher risk of all-cause mortality at 30 days (hazard ratio [HR]: 3.49, 95% confidence interval [CI]: 1.74 to 6.99; p 0.001), 1 year (HR: 3.12, 95% CI: 2.06 to 4.72; p 0.001), and long-term (HR: 2.47, 95% CI: 1.74 to 3.49; p 0.001). Left ventricular ejection fraction (LVEF)40% (odds ratio [OR]: 3.56, 95% CI: 2.24 to 5.65; p 0.001), baseline PASP ≥46 mm Hg (OR: 3.26, 95% CI: 2.07 to 5.12; p 0.001), absence of concomitant tricuspid regurgitation (TR) ≥ moderate (OR: 0.53, 95% CI: 0.34 to 0.84; p 0.001), and logistic EuroSCORE 25% (OR: 1.59, 95% CI: 1.04 to 2.45; p = 0.03) were independent predictors of PASP reduction.In most patients with PH and AS, TAVR is associated with a significant early and late reduction of PASP. Patients with reversible PH after TAVR are at lower risk of all-cause mortality at early, mid-, and long-term follow-up. Therefore, the presence of PH should not preclude treatment with TAVR.

«The future from the past is not the present» (Hans R. Figulla) Recent advances and successes in transcatheter valve technology (TVT) are not necessarily the most reliable and only predictor of the future of this exciting field; drawbacks and surprises are possible and could curb the current optimism in the future. It appears likely, however, that the field shall maintain its momentum with dwindling borderlines between cardiology and heart surgery and growing integration of tissue engineering, material sciences, and cellular biology in transcatheter valve technology (TVT) research and development. In this chapter we focus on the potentials and drawbacks of the present and emerging TVT technology and outline some of the future lines of research and applications.

When the incidence of tricuspid regurgitation is taken into account, along with its impact on functional status and long-term survival, tricuspid regurgitation is currently undertreated. Today, though transcatheter therapy of aortic, mitral- and pulmonic valve disease is well established, interventional treatment of tricuspid valve disease is still in its early stages. Currently, various promising devices are in different stages of development, but it is still too early to clarify which interventional approach in the future might result in functional and clinical success. Similarly, it is yet unclear which type of patient subpopulation will benefit from this type of treatment. Seen in the current context of the overall evolution in the adoption of catheter-based treatments for other types of structural heart disease, the need for and interest in effective interventional treatments for tricuspid regurgitation is growing.

Background and aims Management of chronic rejection is challenging since there are not sufficient preventive or therapeutic strategies. The rejection process leads to overexpression of ED-A + fibronectin (ED-A + Fn). The human antibody F8, specific to ED-A + Fn, may serve as a vehicle for targeted delivery of bioactive payloads, e.g. interleukin 10 (IL-10). The aim of this study was to investigate the therapeutic effects of the fusion protein F8-interleukin-10 (F8-IL10) in the process of chronic rejection development. Methods A heterotopic rat heart transplantation model was used to induce chronic rejection. For therapeutic interventions, the immunocytokines F8-humanIL10 (DEKAVIL), F8-ratIL10 as well as KSF-humanIL10 (irrelevant antigen-specificity) were used. Treatment was performed weekly for 10weeks starting at day 7 after transplantation (1mg/animal). Results In the cardiac allografts, treatment with F8-huIL10 or F8-ratIL10 was associated with increased heart weights, a higher grade of chronic rejection, increased CIF, higher protein expression levels of alpha-smooth muscle actin (α-SMA), an augmented infiltration with inflammatory cells (CD4+, CD8+ and CD68+ cells) and higher serum levels of brain natriuretic peptide (BNP) compared to the control groups. Conclusions All observed treatment effects are transplantation-specific since the F8 antibody is specific to ED-A + Fn that is not expressed in healthy hearts. A clear targeting effect of F8-huIL10 as well as F8-ratIL10 could be proven. Against that background, a further study is needed to address the question, if F8-IL10 treatment is capable to reduce CAV and CIF starting at a time point when chronic rejection has fully developed (therapeutic approach).

Cardiac arrest is the major cause of sudden death in developed countries. Extracorporeal cardiopulmonary resuscitation (ECPR) employs extracorporeal membrane oxygenation (ECMO) in patients without return of spontaneous circulation (ROSC) by conventional cardiopulmonary resuscitation (CPR). Aim of the current study was to assess short- and long-term outcome in patients treated with ECPR in our tertiary center and to identify predictors of outcome. We retrospectively collected data of all patients treated with ECPR at our institution from 2002 to 2013. Outcome was assessed according to patient records; good neurological outcome was defined as cerebral performance category 1 or 2. Quality of life data was collected using EQ-5 questionnaire. Uni- and multivariate analysis was applied to identify predictors of outcome. One-hundred and seventeen patients were included into the study. Weaning from ECMO was successful in 61 (52 %) patients. Thirty-day survival endpoint was achieved by 27 (23 %) patients. Good neurological outcome was present in 17 (15 %) patients. Multivariate analysis revealed baseline serum lactate as the strongest predictor of outcome, whereas age and out-of-hospital CPR did not predict outcome. The optimal lactate cut-off to discriminate outcome was determined at 4.6 mmol/l [HR 3.55 (2.29–5.49), p

In cardiogenic shock (CS), pathophysiological changes include microcirculatory dysfunction, vascular leakage, and an increase in platelet and leukocyte adhesion to the endothelium, as well as endothelial activation and dysfunction. The endothelial glycocalyx has been recognized as a central modulator of these processes. Glycosaminoglycan heparan sulfate is a major component of the glycocalyx of endothelial cells, and syndecan-1 (S1) represents the most prevalent proteoglycan. The aim of the current study was to investigate circulating levels of the glycocalyx components in patients with infarct-related CS. In 184 patients with CS complicating acute myocardial infarction, blood samples were collected at admission and after one day. Intra-aortic balloon pumping was used in 94 patients (51%). Glycosaminoglycan heparan sulfate and S1 were measured using standard enzyme-linked immunosorbent assay kits. All-cause mortality at 30 days was used for outcome assessment. Levels of S1 decreased between days 1 and 2 (339 [interquartile range [QR], 109-852] vs. 220 [IQR, 57-606] ng/mL; P = 0.01). In contrast, glycosaminoglycan heparan sulfate increased over time (1.9 [IQR, 0.3-6.4] vs. 7.1 [IQR, 3.7-11.7] mg/mL; P < 0.001). Survivors at 30 days had lower admission S1 levels (P < 0.001). In multivariable analysis, S1 remained an independent predictor of 30-day mortality (odds ratio per μg/mL, 2.2 [95% confidence interval, 1.30-3.58]; P = 0.003) together with serum lactate, age, and ejection fraction. Increased levels of S1 are an independent predictor of short-term mortality in patients with acute myocardial infarction and CS.ClinicalTrials.gov Identifier: NCT00491036.

This study sought to evaluate the influence of intraaortic balloon pump (IABP) counterpulsation on the microcirculation in patients with cardiogenic shock (CS) complicating acute myocardial infarction. In patients with shock profound alterations of the microcirculation have been observed and their clinical relevance has been described. Different treatment strategies exist to improve microvascular perfusion in patients with CS; however, the role of IABP treatment is not clearly defined. A predefined substudy of the randomized Intraaortic Balloon Pump in Cardiogenic Shock II trial (IABP-SHOCK II) investigated the sublingual microcirculation using a sidestream darkfield intravital microscope on days 1, 2 and 4 after the onset of shock. Perfused capillary (

Fetal variants of tenascin-C are not expressed in healthy adult myocardium. But, there is a relevant re-occurrence during pathologic cardiac tissue and vascular remodeling. Thus, these molecules, in particular B and C domain containing tenascin-C, might qualify as promising novel biomarkers for diagnosis and prognosis estimation. Since a stable extracellular deposition of fetal tenascin-C variants is present in diseased cardiac tissue, the molecules are excellent target structures for antibody-based delivery of diagnostic (e.g., radionuclides) or therapeutic (bioactive payloads) agents directly to the site of disease. Against the background that fetal tenascin-C variants are functionally involved in cardiovascular tissue remodeling, therapeutic functional blocking strategies could be experimentally tested in the future.

Transvaskulare Aortenklappenimplantation (TAVI): effektives, sicheres Behandlungsverfahren fur Patienten mit symptomatischer, hochgradiger Aortenklappenstenose Indikationsstellung: TAVI-Zentren: Durchfuhrung TAVI: Nach TAVI: Zertifizierung

In der Therapie der chronischen Rechtsherzinsuffizienz fuhren die aktuellen Leitlinien der European Society of Cardiology zur Therapie der pulmonalen Hypertonie medikamentose Ansatze ein, die erstmalig auf eine Reduktion der Mortalitat abzielen. Zudem steht mit Riociguat ein neues Medikament fur die Therapie der chronisch thrombembolischen pulmonalen Hypertonie (CTEPH) zur Verfugung. Perkutane Interventionen an den Klappen des rechten Ventrikels sind fur die Pulmonalklappe in der Therapie etabliert, fur die Trikuspidalklappe vielversprechend im experimentellen Stadium. In der Therapie der akuten Rechtsherzinsuffizienz eroffnet die Miniaturisierung der mechanischen extrakorporalen Unterstutzungssysteme sowie die Verwendung von perkutan eingebrachte Perfusionskanulen neue Therapieoptionen auf dem Sektor „Bridge to Recovery“ und „Bridge to Decision“ hin zu langerfristiger Unterstutzung von Herz- und Lungenfunktion.

Background—Transcatheter caval valve implantation is under evaluation as a treatment option for inoperable patients with severe tricuspid regurgitation (TR). The procedure involves the catheter-based implantation of bioprosthetic valves in the inferior vena cava and superior vena cava to treat symptoms associated with TR. This study is the first to evaluate the feasibility, safety, and efficacy of this interventional concept.Methods and Results—Twenty-five patients (mean age, 73.9±7.6 years; women, 52.0%) with severe symptomatic TR despite optimal medical treatment deemed unsuitable for surgery were treated with caval valve implantation under a compassionate clinical use program. Technical feasibility defined as procedural success, hemodynamic effect defined as venous pressure reduction, and safety defined as periprocedural adverse events were evaluated, with clinical follow-up at discharge and up to 12 months. The functional impact was evaluated by assessment of New York Heart Association class at the time of hospital discharge. The total number of valves implanted in the caval position was 31. Patients were treated with single (inferior vena cava-only; n=19; 76.0%) or bicaval valve implantation (inferior vena cava+superior vena cava; n=6; 24.0%). Either balloon-expandable valves (Sapien XT/3: n=18; 72.0%) or self-expandable valves (TricValve: n=6; 24.0%; Directflow: n=1; 4.0%) were used. Procedural success was achieved in 96% (n=24). Early and late valve migration requiring surgical intervention occurred in 1 patient each. Thirty-day and in-hospital mortality were 8% (2 of 25) and 16% (4 of 25). Causes of in-hospital mortality included respiratory (n=1) or multiple organ failure (n=3) and were not linked to the procedure. Mean overall survival in the study cohort was 316±453 days (14–1540 days).Conclusions—Caval valve implantation for the treatment of severe TR and advanced right ventricular failure is associated with a high procedural success rate and seems safe and feasible in an excessive-risk cohort. The study demonstrates hemodynamic efficacy with consistent elimination of TR-associated venous backflow and initial clinical improvement. These results encourage further trials to determine which patients benefit most from this interventional approach.

Severe tricuspid regurgitation (TR) is a complex condition of the right ventricle and tricuspid valve apparatus and frequently associated with symptomatic heart failure and significant morbidity and mortality [(1)][1]. In contrast to other types of valve disease, TR is seldom an isolated valve

Management of acute and especially chronic rejection after human cardiac transplantation is still challenging. Chronic rejection, represented by allograft vasculopathy (CAV) and cardiac interstitial fibrosis (CIF) is known to cause severe long-term complications. Rejection associated tissue-remodelling entails the reoccurrence of fetal variants of Fibronectin (Fn) and Tenascin-C (Tn-C), which are virtually absent in adult human organs. In a rat model, an extensive re-expression could be demonstrated for ED-A(+) Fn with spatial association to CAV and CIF. Thus, it is of great interest to investigate the cardiac tissue expression and distribution in human samples. From 48 heart transplanted patients, 64 tissue specimens derived from right ventricular biopsies were available. Histopathological analysis was performed according to the International Society for Heart and Lung Transplantation (ISHLT) guidelines for the detection of acute rejection. By immunohistochemistry, protein expression of ED-A(+) Fn, B(+) Tn-C, alpha-smooth muscle actin, CD31 and CD45 was assessed and analysed semiquantitatively. Co-localisation studies were performed by means of immunofluorescence double labelling. Histopathological analysis of the 64 samples revealed different ISHLT grades (0R in 36 cases, 1R in 20 cases and 2R in 8 cases). There was a distinct and quantitatively relevant re-occurrence of ED-A(+) Fn and B(+) Tn-C in most samples. Semi-quantitative evaluation did not show any correlation to the acute rejection grade for all markers. Interestingly, significant correlations to the extent of inflammation could be shown for ED-A(+) Fn (r = 0.442, p = 0.000) and B(+) Tn-C (r = 0.408, p = 0.001) as well as between both proteins (r = 0.663, p = 0.000). A spatial association of ED-A(+) Fn and B(+) Tn-C to CAV and CIF could be demonstrated. A relevant re-occurrence of ED-A(+) Fn and B(+) Tn-C following human heart transplantation could be demonstrated with spatial association to signs of rejection and a significant correlation to tissue inflammation. These data might contribute to the identification of novel biomarkers reflecting the rejection process and to the development of promising strategies to image, prevent or treat cardiac rejection.

Severe tricuspid regurgitation (TR) frequently constitutes a high risk for surgical correction.1 For inoperable patients with TR, transcatheter caval valve implantation has been suggested.2 Herein, we report the human application and 12-month follow-up after first bicaval implantation of self- expanding valves into the superior (SVC) and inferior (IVC) vena cava as interventional concept for severe TR.3 The procedure was performed as compassionate treatment in an 83-year-old female with severe, long-standing functional and structural TR after University Hospital Jena institutional review board approval. At admission, she was in New York Heart Association-stage IV and presented symptoms of chronic right heart failure with peripheral edema, ascites, and orthopnea. Synthetic liver function was impaired with reduced serum albumin and cholinesterase because of congestive hepatopathy, echocardiography demonstrated right ventricle enlargement with preserved systolic function. Right heart catheterization confirmed severe TR with a ventricular wave (v-wave) in the right atrium (RA), the SVC, and the IVC of 32, 27, and 28 mm Hg, respectively, as well as a slightly elevated pulmonary artery pressure and vascular resistance. Hemodynamics, laboratory, and clinical parameters are detailed in the Table. View this table: Table. Clinical and Hemodynamic Parameters Before and After Caval Valve Implantation Based on computed tomography-angiographic images, 2 self-expanding percutaneous heart valves were custom-made with 10% to 20% oversizing to fit the anticipated implantation site in the SVC and IVC.4 The IVC valve was designed with the upper segment protruding into the RA with the biological valve located above …

Transcatheter aortic valve implantation (TAVI) has become an established procedure for patients with aortic valve stenosis and significant comorbidities. One option offered by this technique is the implantation of a transcatheter valve inside a surgically implanted bioprosthesis. Many reports address the feasibility but also the pitfalls of these valve-in-valve (VIV) procedures. Review articles provide tables listing which valve sizes are appropriate based on the size of the initially implanted bioprosthesis. However, we previously argued that the hemodynamic performance of a prosthetic tissue valve is in large part a result of the dimensions of the bioprosthesis in relation to the patient's aortic outflow dimensions. Thus, the decision if a VIV TAVI procedure is likely to be associated with a favorable hemodynamic result cannot safely be made by looking at premade sizing tables that do not include patient dimensions and do not inquire about the primary cause for bioprosthetic valve stenosis. Prosthesis-patient mismatch (PPM) may therefore be more frequent than expected after conventional aortic valve replacement. Importantly, it may be masked by a potentially flawed method assessing its relevance. Such PPM may therefore impact significantly on hemodynamic outcome after VIV TAVI. Fifteen percent of currently published VIV procedures show only a minimal reduction of pressure gradients. We will address potential pitfalls in the current determination of PPM, outline the missing links for reliable determination of PPM, and present a simplified algorithm to guide decision making for VIV TAVI.

BACKGROUND: Caval valve implantation has been suggested for transcatheter treatment of severe tricuspid regurgitation (TR). Combining the interventional technique with the promising surgical experience with decellularized valves, we sought to evaluate the functional and structural outcome of decellularized pericardial tissue valves (dTVs) in the low-pressure venous circulation in a chronic model of TR. METHODS AND RESULTS: Sixteen pericardial tissue valves were heterotopically implanted in the inferior and superior vena cava in a sheep model (54–98 kg; median 74.5 kg, n = 8) of severe TR. The devices were assembled using self-expanding nitinol stents and bovine pericardia decellularized by a detergent-based protocol (group dTV; n = 8). Glutaraldehyde-fixed pericardial tissue valves served as control (GaTV, n = 8). After 6 months, device function and structural maturation were analyzed using echocardiographic, histologic, immunohistologic, and electron microscopic approaches. After implantation, cardiac output increased significantly from 3.7 ± 1.1 l/min to 4.8 ± 1.1 l/min (P