Transcatheter or Surgical Treatment of Aortic-Valve Stenosis.

BACKGROUND: Among low-risk patients with severe, symptomatic aortic stenosis who are eligible for both transcatheter aortic-valve implantation (TAVI) and surgical aortic-valve replacement (SAVR), data are lacking on the appropriate treatment strategy in routine clinical practice. METHODS: In this randomized noninferiority trial conducted at 38 sites in Germany, we assigned patients with severe aortic stenosis who were at low or intermediate surgical risk to undergo either TAVI or SAVR. Percutaneous- and surgical-valve prostheses were selected according to operator discretion. The primary outcome was a composite of death from any cause or fatal or nonfatal stroke at 1 year. RESULTS: A total of 1414 patients underwent randomization (701 to the TAVI group and 713 to the SAVR group). The mean (±SD) age of the patients was 74±4 years; 57% were men, and the median Society of Thoracic Surgeons risk score was 1.8% (low surgical risk). The Kaplan-Meier estimate of the primary outcome at 1 year was 5.4% in the TAVI group and 10.0% in the SAVR group (hazard ratio for death or stroke, 0.53; 95% confidence interval [CI], 0.35 to 0.79; P<0.001 for noninferiority). The incidence of death from any cause was 2.6% in the TAVI group and 6.2% in the SAVR group (hazard ratio, 0.43; 95% CI, 0.24 to 0.73); the incidence of stroke was 2.9% and 4.7%, respectively (hazard ratio, 0.61; 95% CI, 0.35 to 1.06). Procedural complications occurred in 1.5% and 1.0% of patients in the TAVI and SAVR groups, respectively. CONCLUSIONS: Among patients with severe aortic stenosis at low or intermediate surgical risk, TAVI was noninferior to SAVR with respect to death from any cause or stroke at 1 year. (Funded by the German Center for Cardiovascular Research and the German Heart Foundation; DEDICATE-DZHK6 ClinicalTrials.gov number, NCT03112980.).

European Society for Organ Transplantation (ESOT) Consensus Statement on the Use of Non-invasive Biomarkers for Cardiothoracic Transplant Rejection Surveillance.

While allograft rejection (AR) continues to threaten the success of cardiothoracic transplantation, lack of accurate and repeatable surveillance tools to diagnose AR is a major unmet need in the clinical management of cardiothoracic transplant recipients. Endomyocardial biopsy (EMB) and transbronchial biopsy (TBBx) have been the cornerstone of rejection monitoring since the field's incipience, but both suffer from significant limitations, including poor concordance of biopsy interpretation among pathologists. In recent years, novel molecular tools for AR monitoring have emerged and their performance characteristics have been evaluated in multiple studies. An international working group convened by ESOT has reviewed the existing literature and provides a series of recommendations to guide the use of these biomarkers in clinical practice. While acknowledging some caveats, the group recognized that Gene-expression profiling and donor-derived cell-free DNA (dd-cfDNA) may be used to rule out rejection in heart transplant recipients, but they are not recommended for cardiac allograft vasculopathy screening. Other traditional biomarkers (NT-proBNP, BNP or troponin) do not have sufficient evidence to support their use to diagnose AR. Regarding lung transplant, dd-cfDNA could be used to rule out clinical rejection and infection, but its use to monitor treatment response is not recommended.

Impact of Different Valve-in-Valve Positions on Functional Results of the New Generation of Balloon-Expandable Transcatheter Heart Valve.

OBJECTIVES: Very precise positioning of the transcatheter heart valve (THV) inside the degenerated SAV is a crucial factor for valve-in-valve (ViV) procedure to achieve optimal hemodynamic results. Therefore, our study aimed to investigate the impact of implantation depth on functional results after ViV procedures in a standardized in vitro setting. METHODS: THV (SAPIEN 3 Ultra 23-mm size) and three SAV models (Magna Ease, Trifecta, and Hancock II-all 21-mm size) were tested at different circulatory conditions in five different positions of the THV (2-6 mm) inside the SAV. Mean pressure gradient (MPG), effective orifice area (EOA), geometric orifice area (GOAmax), and pinwheeling index (PWImean) were analyzed. RESULTS: EOA and MPG of the THV did not differ significantly regarding the position inside the Magna Ease and the Hancock II (p > 0.05). However, EOA differed significantly, depending on the position of the THV inside Trifecta (2 vs. 5 mm; p = 0.021 and 2 vs. 6 mm; p < 0.001). The THV presented the highest EOA (2.047 cm2) and the lowest MPG (5.387 mm Hg) inside the Magna Ease, whereas the lowest EOA (1.335 cm2) and the highest MPG (11.876 mm Hg) were shown inside the Hancock II. Additionally, the highest GOAmax and the lowest PWImean of the THV were noticed inside the Magna Ease. The THV showed lower GOAmax and higher PWImean inside the Trifecta when placed in a deeper position. CONCLUSION: Deep implantation of the SAPIEN 3 Ultra inside the Trifecta correlates with impaired functional results. In contrast, the implantation position of the SAPIEN 3 Ultra inside the Magna Ease and the Hancock II did not have a significant effect on functional results.

New insights into the hemodynamics of pulmonary homograft patients under stress echocardiography: The contribution of pressure recovery.

BACKGROUND: The importance of pulmonary artery pressure recovery (PR) in patients with Ross procedures in whom a homograft substitutes the resected pulmonary valve, is unknown. The aim of the study was to evaluate the occurrence and extent of PR in the pulmonary artery in 65 asymptomatic patients with pulmonary homograft after Ross surgery during rest and exercise. METHODS: Stress echocardiography was performed in 65 pulmonary homograft patients and 31 controls with native pulmonary valves up to 75 W. Right ventricular systolic pressure (RVSP), transvalvular flow, mean pressure gradient (Pmean ), valve resistance, and RV stroke work were determined in the exercise (max. 75 W) and recovery phases in increments of 25 W each. RESULTS: Pulmonary homografts demonstrated significantly elevated Pmean compared to controls at all stages. When considering pressure recovery (absolute and relative PR at rest 3.8 ± 1.8 mm Hg, 42.6 ± 7.2%, respectively) and transvalvular energy loss (EL; at rest 4.5 ± 4.3 mm Hg) the homograft hemodynamics reached the level of controls. In a subgroup of patients with tricuspid regurgitation, resting RVSP was the same in homograft patients and controls (21.3 ± 6.1 vs. 20.4 ± 6.3, p = .62), despite significant different Pmax values. CONCLUSIONS: Ross patients with pulmonary homograft showed systematically increased hemodynamic parameters compared to normal pulmonary valves. These differences were abolished when PR was considered for homograft patients. The equality of RVSP values at rest in both groups shows non-invasive evidence for PR in the pulmonary system after homograft implantation. Therefore, PR appears to be an important measure in calculating the actual hemodynamics in pulmonary homografts.

[Recommendations of the S3 Guideline "Use of Extracorporeal Circulation (ECLS/ ECMO) for Cardiac and Circulatory Failure" of the Association of Scientific Medical Societies in Germany]. / Empfehlungen der S3-Leitlinie (AWMF) "Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen".

In recent years, the use of mechanical support for patients with cardiac or circulatory failure has continuously increased, leading to 3,000 ECLS/ECMO (extracorporeal life support/extracorporeal membrane oxygenation) implantations annually in Germany. Due to the lack of guidelines, there is an urgent need for evidence-based recommendations addressing the central aspects of ECLS/ECMO therapy. In July 2015, the generation of a guideline level S3 according to the standards of the Association of the Scientific Medical Societies in Germany (AWMF) was announced by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS). In a well-structured consensus process, involving experts from Germany, Austria and Switzerland, delegated by 16 scientific societies and the patients' representation, the guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" was created under guidance of the GSTCVS, and published in February 2021. The guideline focuses on clinical aspects of initiation, continuation, weaning and aftercare, herein also addressing structural and economic issues. This article presents an overview on the methodology as well as the final recommendations.

Impact of high-pressure balloon aortic valvuloplasty on the hydrodynamic result after a transcatheter valve-in-valve procedure.

OBJECTIVES: The aim of this study was to investigate the degree of functional improvement of a transcatheter heart valve (THV) for valve-in-valve after bioprosthetic valve fracture (BVF) of three small surgical aortic valve bioprostheses (SAVBP) using high-pressure balloon aortic valvuloplasty (HP-BAV) under standardized ex-vivo-conditions. METHODS: A THV 26 mm (Evolut R) and SAVBP 21 mm (Perimount Magna Ease, Trifecta, and Epic supra [n = 4] were used. Mean pressure gradient (MPG), effective orifice area (EOA), geometric orifice area (GOA), minimal internal diameter (MID), and pinwheeling index (PWI) were analyzed before and after HP-BAV of the SAVBP using a noncompliant balloon. Fracturing of the SAVBP was done before implantation of the THV and the balloon pressures at the point of fracture were recorded. RESULTS: The Magna Ease and Epic fractured at balloon pressures of 18 and 8 atm, respectively. The Trifecta did not fracture up to a balloon pressure of 30 atm but was dilated. HP-BAV led to increased THV expansion as evident by straightened coaptation lines of the Evolut R 26 mm with reduced PWI, increased MID, and increased GOA in all 21 mm SAVBP. Evolut R showed significantly lower MPG and higher EOA as ViV in all prostheses after HP-BAV (p < 0.001). MPG and EOA of Evolut R differed regarding the SAVBP. Evolut R presented the lowest MPG and highest EOA in Magna Ease and the highest MPG and lowest EOA in Epic supra. CONCLUSIONS: The degree of function improvement of the same THV as ViV after HP-BAV depends on the surgical valve model. Functional improvement can also be achieved without valve fracture.

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline]. / Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen : Kurzversion der AWMF-S3-Leitlinie.

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.

Patients at low surgical risk as defined by the Society of Thoracic Surgeons Score undergoing isolated interventional or surgical aortic valve implantation: in-hospital data and 1-year results from the German Aortic Valve Registry (GARY).

AIMS: Transcatheter aortic valve implantation (TAVI) has become the standard treatment for patients with severe aortic valve stenosis at high surgical risk and may be considered for patients with intermediate risk. During the last few years, an increasing number of patients with low surgical risk have been treated with TAVI. In this study, low-risk patients undergoing isolated TAVI or surgical aortic valve replacement (SAVR) were analysed using data from the German Aortic Valve Registry (GARY). METHODS AND RESULTS: All patients with a Society of Thoracic Surgeons Score of <4% undergoing TAVI or SAVR in 2014 and 2015 were evaluated. A total of 20 549 low surgical risk patients remained for further analysis, comprising 14 487 surgical patients and 6062 TAVI patients. Since TAVI patients were significantly older and had significantly more co-morbidities, a weighted propensity score model was used to compare SAVR and TAVI patients for in-hospital, 30-day, and 1-year mortality. Transcatheter aortic valve implantation patients showed a significantly higher in-hospital and 30-day survival than SAVR patients (in hospital survival TAVI vs. SAVR: 98.5% vs. 97.3%; P = 0.003; 30-day survival TAVI vs. SAVR: 98.1% vs. 97.1%; P = 0.014). At 1 year, survival rates did not differ significantly (survival TAVI vs. SAVR: 90.0% vs. 91.2%; P = 0.158). CONCLUSION: In this first GARY analysis of low-risk patients, weighted comparison showed similar 1-year survival for TAVI and SAVR and higher in-hospital survival for TAVI patients.

Outcomes of transcatheter mitral valve replacement for degenerated bioprostheses, failed annuloplasty rings, and mitral annular calcification.

Aims: We sought to evaluate the outcomes of transcatheter mitral valve replacement (TMVR) for patients with degenerated bioprostheses [valve-in-valve (ViV)], failed annuloplasty rings [valve-in-ring (ViR)], and severe mitral annular calcification [valve-in-mitral annular calcification (ViMAC)]. Methods and results: From the TMVR multicentre registry, procedural and clinical outcomes of ViV, ViR, and ViMAC were compared according to Mitral Valve Academic Research Consortium (MVARC) criteria. A total of 521 patients with mean Society of Thoracic Surgeons score of 9.0 ± 7.0% underwent TMVR (322 patients with ViV, 141 with ViR, and 58 with ViMAC). Trans-septal access and the Sapien valves were used in 39.5% and 90.0%, respectively. Overall technical success was excellent at 87.1%. However, left ventricular outflow tract obstruction occurred more frequently after ViMAC compared with ViR and ViV (39.7% vs. 5.0% vs. 2.2%; P < 0.001), whereas second valve implantation was more frequent in ViR compared with ViMAC and ViV (12.1% vs. 5.2% vs. 2.5%; P < 0.001). Accordingly, technical success rate was higher after ViV compared with ViR and ViMAC (94.4% vs. 80.9% vs. 62.1%; P < 0.001). Compared with ViMAC and ViV groups, ViR group had more frequent post-procedural mitral regurgitation ≥moderate (18.4% vs. 13.8% vs. 5.6%; P < 0.001) and subsequent paravalvular leak closure (7.8% vs. 0.0% vs. 2.2%; P = 0.006). All-cause mortality was higher after ViMAC compared with ViR and ViV at 30 days (34.5% vs. 9.9% vs. 6.2%; log-rank P < 0.001) and 1 year (62.8% vs. 30.6% vs. 14.0%; log-rank P < 0.001). On multivariable analysis, patients with failed annuloplasty rings and severe MAC were at increased risk of mortality after TMVR [ViR vs. ViV, hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.27-3.12; P = 0.003; ViMAC vs. ViV, HR 5.29, 95% CI 3.29-8.51; P < 0.001]. Conclusion: The TMVR provided excellent outcomes for patients with degenerated bioprostheses despite high surgical risk. However, ViR and ViMAC were associated with higher rates of adverse events and mid-term mortality compared with ViV.

Patients at Intermediate Surgical Risk Undergoing Isolated Interventional or Surgical Aortic Valve Implantation for Severe Symptomatic Aortic Valve Stenosis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is increasingly being used for treatment of severe aortic valve stenosis in patients at intermediate risk for surgical aortic valve replacement (SAVR). Currently, real-world data comparing indications and clinical outcomes of patients at intermediate surgical risk undergoing isolated TAVR with those undergoing SAVR are scarce. METHODS: We compared clinical characteristics and outcomes of patients with intermediate surgical risk (Society of Thoracic Surgeons score 4%-8%) who underwent isolated TAVR or conventional SAVR within the prospective, all-comers German Aortic Valve Registry. RESULTS: A total of 7613 patients at intermediate surgical risk underwent isolated TAVR (n=6469) or SAVR (n=1144) at 92 sites in Germany between 2012 and 2014. Patients treated by TAVR were significantly older (82.5±5.0 versus 76.6±6.7 years, P<0.001) and had higher risk scores (logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation]: 21.2±12.3% versus 14.2±9.5%, P<0.001; Society of Thoracic Surgeons score: 5.6±1.1 versus 5.2±1.0, P<0.001). Multivariable analyses revealed that advanced age, coronary artery disease, New York Heart Association class III/IV, pulmonary hypertension, prior cardiac decompensation, elective procedure, arterial occlusive disease, no diabetes mellitus, and a smaller aortic valve area were associated with performing TAVR instead of SAVR (all P<0.001). Unadjusted in-hospital mortality rates were equal for TAVR and SAVR (3.6% versus 3.6%, P=0.976), whereas unadjusted 1-year mortality was significantly higher in patients after TAVR (17.5% versus 10.8%, P<0.001). After propensity score matching, the difference in 1-year mortality between patients with TAVR and SAVR was no longer significant (17.1% versus 15.7%, P=0.59). CONCLUSIONS: Patients at intermediate risk undergoing TAVR differ significantly from those treated with SAVR with regard to age and baseline characteristics. Isolated TAVR and SAVR were associated with an in-hospital mortality rate of 3.6%. In the propensity score analysis, there was no significant difference in 1-year mortality between patients with TAVR and SAVR.

Prognostic Factors for Long-Term Survival after Surgical Resection of Primary Cardiac Sarcoma.

BACKGROUND: Primary cardiac sarcoma (CS) is an extremely rare disease. This study aims to identify possible prognostic factors for long-term survival. METHODS: A total of 17 consecutive patients who were treated for primary CS between 2003 und 2018 at two cardiac centers were investigated. Clinical data and histological characteristics of the tumors were analyzed. Long-term follow-up of all patients were performed. RESULTS: The median age was 54 years (range: 23-74). The tumors originated from the left side of the heart in nine patients. Histologically, there were four angiosarcomas, three intimal sarcomas, and three synovial sarcomas. One- and 7-year survivals were 81.9 and 18.2%, respectively. Low expression levels of Ki-67 tended to be associated with increased survival (log-rank p = 0.06). Adjuvant chemotherapy but not radiotherapy regardless of existing metastases was associated with significantly increased survival (log-rank p = 0.001). CONCLUSION: Angiosarcoma was the most common type of CS. The survival of CS patients is poor but prognostic factors, such as Ki-67, may help estimate the course of the disease. Survival could be improved significantly with chemotherapy.

In vitro 4D Flow MRI evaluation of aortic valve replacements reveals disturbed flow distal to biological but not to mechanical valves.

BACKGROUND AND AIM OF THE STUDY: Aortic hemodynamics influence the integrity of the vessel wall and cardiac afterload. The aim of this study was to compare hemodynamics distal to biological (BV) and mechanical aortic valve (MV) replacements by in vitro 4D Flow MRI excluding confounding factors of in-vivo testing potentially influencing hemodynamics. METHODS: Two BV (Perimount MagnaEase [Carpentier-Edwards], Trifecta [Abbott]) and two MV (On-X [CryoLife], prototype trileaflet valve) were scanned in a flexible aortic phantom at 3T using a recommended 4D Flow MR sequence. A triphasic aortic flow profile with blood-mimicking fluid was established. Using GTFlow (Gyrotools), area and velocity of the ejection jet were measured. Presence and extent of sinus vortices and secondary flow patterns were graded on a 0 to 3 scale. RESULTS: A narrow, accelerated central ejection jet (Area = 27 ± 7% of vessel area, Velocity = 166 ± 13 cm/s; measured at sinotubular junction) was observed in BV as compared to MV (Area = 53 ± 13%, Velocity = 109 ± 21 cm/s). As opposed to MV, the jet distal to BV impacted the outer curvature of the ascending aorta and resulted in large secondary flow patterns (BV: n = 4, grades 3, 3, 2, 1; MV: n = 1, grade 1). Sinus vortices only formed distal to MV. Although physiologically configured, they were larger than normal (grade 3). CONCLUSIONS: In contrast to mechanical valves, biological valve replacements induced accelerated and increased flow patterns deviating from physiological ones. While it remains speculative whether this increases the risk of aneurysm formation through wall shear stress changes, findings are contrasted by almost no secondary flow patterns and typical, near-physiological sinus vortex formation distal to mechanical valves.

Defibrillator-Heart Pump: An Implantable Ventricular Assist Device With Integrated Defibrillator Component-The First In Vitro Testing.

Left ventricular assist devices (LVADs) are an important therapeutic option for patients with end-stage heart failure waiting for heart transplantation or in older patients as definite therapy for heart failure. Interestingly, about 62% of patients receiving LVADs do not have an automatic implantable cardioverter-defibrillator (AICD) at the time of implantation, although these patients have increased risk of being confronted with dangerous arrhythmia. Therefore, an LVAD system including AICD function is a reasonable alternative for such heart failure patients thereby avoiding a second surgical intervention for AICD implantation. In this article, a newly developed system including LVAD and AICD function is introduced, and we also report its first in vitro testing.

Valve-in-valve transcatheter aortic valve implantation with CoreValve/Evolut R© for degenerated small versus bigger bioprostheses.

OBJECTIVES: We present our single center experience with Medtronic CoreValve and Evolut R regarding procedural outcome and 3 years follow-up in patients with degenerated bioprostheses. METHODS: From 1645 patients who underwent transfemoral TAVI at our institution between February 2009 and December 2016, 37 patients with degenerated bioprosthesis were treated with Medtronic CoreValve/Evolut R. All data concerning baseline characteristic, procedural outcomes and follow-up were entered into a dedicated database. RESULTS: Mean age was 83.9 ± 4.4 years and patients showed an average logistic EuroSCORE of 33.2 ± 16.7%. Successful ViV deployment was achieved in all cases, a permanent pacemaker was implanted in 16.2%, no periinterventional stroke and no coronary obstruction occurred. Mortality at 30 days was 2.7%, at 1-year follow-up 5.7% and at three years 13.5%. Depending on bioprosthesis size <23 mm versus ≥23 mm echocardiographic mean gradients post implantation were significantly higher in the smaller bioprostheses, 22.8 mmHg ± 9.4 mmHg versus 15.1 ± 7.1, P = 0.013. CONCLUSION: ViV-TAVI with CoreValve/R is demonstrated to be safe and effective in terms of no coronary obstruction and very low mortality up to 3 years despite slightly higher mean transprosthetic gradients especially in very small bioprostheses.

New Targets for the Prevention of Chronic Rejection after Thoracic Organ Transplantation.

The gold standard for the treatment of terminal heart failure and irreversible lung diseases includes thoracic organ transplantation. The major obstacle for long-term survival after successful transplantation is chronic rejection, an ongoing immunomodulatory disease so far without effective therapy. Therefore, the aim of this review is to elucidate scientific efforts targeting different new mechanisms of cardiac allograft vasculopathy (CAV) and chronic lung allograft dysfunction (CLAD). For this purpose, we performed a systematic review of the literature to assess recent strategies in transplant immunology research. We searched MEDLINE from 2015 up to date for articles addressing the following keywords: CAV, transplant vasculopathy, transplant arteriosclerosis, CLAD, bronchiolitis obliterans transplant, and obliterative bronchiolitis transplant. All articles including experimental models in the field of transplant immunology addressing new aspects for the prevention of chronic rejection after heart and lung transplantation were included in this review. The prevention of chronic rejection would clearly improve the survival of patients after heart and lung transplantation. Interesting targets were addressed in recent research, but further research is necessary to effectively treat this life-threatening disease in transplant recipients.

Impact of procedure-related conduction disturbances after transcatheter aortic valve implantation on myocardial performance and survival evaluated by conventional and speckle tracking echocardiography.

OBJECTIVES: Although procedure-related new cardiac conduction disturbances (CCDs) remain an important issue in transcatheter aortic valve implantation (TAVI), their effect on myocardial function and overall patient outcome remains unclear. The goal of this study was to analyze the influence of procedure-related CCDs on systolic and diastolic LV performance and on patient survival after TAVI. METHODS AND RESULTS: Ninety-five patients who underwent TAVI for severe symptomatic aortic stenosis (AS) and had a complete follow-up were evaluated with respect to procedure-related CCDs. Left ventricular (LV) performance was measured using standard echocardiographic parameters and speckle tracking analysis. Survival was assessed during longer-term follow-up (mean: 29.1 ± 16.9 months). After TAVI, the improvement of global LV function expressed as ejection fraction (LVEF; from 45.5 ± 10.0 to 47.8 ± 13.9%, P = .13) was not significant. New CCDs were found in 35.7% of TAVI recipients. A comparison between patients with and without new CCDs showed that LV systolic function improved in those without CCDs, while it tended to deteriorate in patients with CCDs (change in LVEF: 5.5 ± 12.3% vs -4.9% ± 11.5%, P = .001; change in global longitudinal strain (GLS): -1.1 ± 4.6% vs 1.2 ± 4.5%, P = .01). Changes in diastolic function did not differ significantly between the groups (changes in transmitral E/A-ratio: -0.3 ± 0.6 vs -0.5 ± 0.5, P = .1). Kaplan-Meier survival analysis revealed no significant differences between the two cohorts (P = .795). CONCLUSION: Procedure-related conduction abnormalities after TAVI lead to an LBBB-related dyssynchrony with impairment of LV performance but not of overall survival.

Transcatheter Aortic Valve Implantation in Nonagenarians: Procedural Outcome and Mid-Term Results.

BACKGROUND: For nonagenarians with symptomatic severe aortic stenosis transcatheter aortic valve implantation (TAVI) has become a feasible therapeutic option. Therefore, the aim of this study was to evaluate the procedural outcomes and mid-term follow-up in this patient group and compare this to octogenarians. METHODS: From 1359 patients who underwent TAVI at our institution between March 2009 and February 2016, 82 patients were nonagenarians and 912 were octogenarians. In nonagenarians, mean age was 91.9±1.4years and compared to octogenarians showed a significantly higher logistic EuroScore (27.7±14.8% vs. 23.1±14.4, p=0.005) and STS Score (8.5±4.8% vs. 6.3±6.7, p=0.001). RESULTS: There were no significant differences with regard to stroke rate, pacemaker implantation rate and major vascular complications between the two groups. Thirty-day mortality was 9.8% in nonagenarians and 4.1% in octogenarians (p=0.04). At 1 year, all-cause mortality increased to 30.9% vs. 18.6% (n.s.). CONCLUSION: Nonagenarians showed an increased periprocedural mortality during TAVI and higher mortality in follow-up compared to octogenarians. Age alone is not a predictive factor but indication for treatment should be carefully evaluated by the heart team on an individual basis.

The Impact of Non-Lethal Single-Dose Radiation on Tumor Invasion and Cytoskeletal Properties.

Irradiation is the standard therapy for glioblastoma multiforme. Glioblastoma are highly resistant to radiotherapy and the underlying mechanisms remain unclear. To better understand the biological effects of irradiation on glioblastoma cells, we tested whether nonlethal irradiation influences the invasiveness, cell stiffness, and actin cytoskeleton properties. Two different glioblastoma cell lines were irradiated with 2 Gy and changes in mechanical and migratory properties and alterations in the actin structure were measured. The invasiveness of cell lines was determined using a co-culture model with organotypic hippocampal slice cultures. Irradiation led to changes in motility and a less invasive phenotype in both investigated cell lines that were associated with an increase in a "generalized stiffness" and changes in the actin structure. In this study we demonstrate that irradiation can induce changes in the actin cytoskeleton and motility, which probably results in reduced invasiveness of glioblastoma cell lines. Furthermore, "generalized stiffness" was shown to be a profound marker of the invasiveness of a tumor cell population in our model.

Valve-in-valve using an Edwards Sapien XT into a JenaValve in a patient with a low originating left coronary artery and a heavily calcified aorta.

Coronary obstruction during transcatheter aortic valve implantation is a potentially life-threatening complication. Most of the widely used transcatheter heart valves require a certain distance between the basal aortic annular plane and the origins of the coronary arteries. We report the case of a successful valve-in-valve procedure with an Edwards SAPIEN XT valve into a JenaValve as a bail-out procedure in a patient with a low originating left coronary artery and a heavily calcified aorta.

Clopidogrel significantly lowers the development of atherosclerosis in ApoE-deficient mice in vivo.

The anti-platelet drug clopidogrel has been shown to modulate adhesion molecule and cytokine expression, both playing an important role in the pathogenesis of atherosclerosis. The aim of this study was to investigate the impact of clopidogrel on the development and progression of atherosclerosis. ApoE(-/-) mice fed an atherogenic diet (cholesterol: 1 %) for 6 months received a daily dose of clopidogrel (1 mg/kg) by i.p. injection. Anti-platelet treatment was started immediately in one experimental group, and in another group clopidogrel was started 2 month after beginning of the atherogenic diet. Blood was analysed at days 30, 60 and 120 to monitor the lipid profile. After 6 months the aortic arch and brachiocephalic artery were analysed by Sudan IV staining for plaque size and by morphometry for luminal occlusion. Serum levels of various adhesion molecules were investigated by ELISA and the cellular infiltrate was analysed by immunofluorescence. After daily treatment with 1 mg/kg clopidogrel mice showed a significant reduction of atherosclerotic lesions in the thoracic aorta and within cross sections of the aortic arch [plaque formation 55.2 % (clopidogrel/start) vs. 76.5 % (untreated control) n = 8, P < 0.05]. After treatment with clopidogrel P-/E-selectin levels and cytokine levels of MCP-1 and PDGFß were significantly reduced as compared to controls. The cellular infiltrate showed significantly reduced macrophage and T-cell infiltration in clopidogrel-treated animals. These results show that clopidogrel can effectively delay the development and progression of 'de-novo' atherosclerosis. However, once atherosclerotic lesions were already present, anti-platelet treatment alone did not result in reverse remodelling of these lesions.