Guideline adherence in the use of coronary angiography in patients presenting at the emergency department without myocardial infarction - Results from the German ENLIGHT-KHK project.

Background: For patients with acute myocardial infarction (AMI), direct coronary angiography (CA) is recommended, while for non-AMI patients, the diagnostic work-up depends on clinical criteria. This analysis provides initial prospective German data for the degree of guideline-adherence (GL) in the use of CA on non-AMI patients presenting at the emergency department (ED) with suspected acute coronary syndrome (ACS) according to the 2015 ESC-ACS-GL. Furthermore the implications of the application of the 2020 ESC-ACS-GL recommendations were evaluated. Methods: Patient symptoms were identified using a standardized questionnaire; medical history and diagnostic work-up were acquired from health records. In accordance with the 2015 ESC-ACS-GL, CA was considered GL-adherent if intermediate risk criteria (IRC) were present or non-invasive, image-guided testing (NIGT) was pathological. Results: Between January 2019 and August 2021, 229 patients were recruited across seven centers. Patients presented with chest pain, dyspnea, and other symptoms in 66.7%, 16.2% and 17.1%, respectively, were in mean 66.3 ± 10.5 years old, and 36.3% were female. In accordance with the 2015 ESC-ACS-GL, the use of CA was GL-adherent for 64.0% of the patients. GL-adherent compared to non-adherent use of CA resulted in revascularization more often (44.5% vs. 17.1%, p < 0.001). Applying the 2020 ESC-ACS-GL, 20.4% of CA would remain GL-adherent. Conclusions: In the majority of cases, the use of CA was adherent to the 2015 ESC-ACS-GL. With regard to the 2020 and 2023 ESC-ACS-GL, efforts to expand the utilization of NIGT are crucial, especially as GL-adherent use of CA is more likely to result in revascularization.(German Clinical Trials Register DRKS00015638; https://drks.de/search/de/trial/DRKS00015638; (registration date: 19 February 2019)).

3D bioprinting ofE. coliMG1655 biofilms on human lung epithelial cells for building complexin vitroinfection models.

Biofilm-associated infections are causing over half a million deaths each year, raising the requirement for innovative therapeutic approaches. For developing novel therapeutics against bacterial biofilm infections, complexin vitromodels that allow to study drug effects on both pathogens and host cells as well as their interaction under controlled, physiologically relevant conditions appear as highly desirable. Nonetheless, building such models is quite challenging because (1) rapid bacterial growth and release of virulence factors may lead to premature host cell death and (2) maintaining the biofilm status under suitable co-culture requires a highly controlled environment. To approach that problem, we chose 3D bioprinting. However, printing living bacterial biofilms in defined shapes on human cell models, requires bioinks with very specific properties. Hence, this work aims to develop a 3D bioprinting biofilm method to build robustin vitroinfection models. Based on rheology, printability and bacterial growth, a bioink containing 3% gelatin and 1% alginate in Luria-Bertani-medium was found optimal forEscherichia coliMG1655 biofilms. Biofilm properties were maintained after printing, as shown visually via microscopy techniques as well as in antibiotic susceptibility assays. Metabolic profile analysis of bioprinted biofilms showed high similarity to native biofilms. After printing on human bronchial epithelial cells (Calu-3), the shape of printed biofilms was maintained even after dissolution of non-crosslinked bioink, while no cytotoxicity was observed over 24 h. Therefore, the approach presented here may provide a platform for building complexin vitroinfection models comprising bacterial biofilms and human host cells.

Evaluation of the guideline-adherence of coronary angiography in patients with suspected chronic coronary syndrome - Results from the German prospective multicentre ENLIGHT-KHK project.

Background: With 900'000 coronary angiographies (CA) per year, Germany has the highest annual per capita volume in Europe. Until now there are no prospective clinical data on the degree of guideline-adherence in the use of CA in patients with suspected chronic coronary syndrome (CCS) in Germany. Methods: Between January 2019 and August 2021, 458 patients with suspected CCS were recruited in nine German centres. Guideline-adherence was evaluated according to the current European Society of Cardiology and German guidelines. Pre-test probability (PTP) for CAD was determined using age, gender, and a standardized patient questionnaire to identify symptoms. Data on the diagnostic work-up were obtained from health records. Results: Patients were in mean 66.6 years old, male in 57.3 %, had known CAD in 48.4 % and presented with typical, atypical, non-anginal chest pain or dyspnoea in 35.7 %, 41.3 %, 23.0 % and 25.4 %, respectively. PTP according to the European guidelines was in mean 24.2 % (11.9 %-36.5 % 95 % CI). 20.9 % of the patients received guideline-recommended preceding non-invasive image guided testing. The use of CA was adherent to the European and German guideline recommendations in 20.4 % and 25.4 %, respectively. In multivariate-analysis, arterial hypertension and prior revascularization were predictors of guideline non-adherence. Conclusion: These are the first prospective clinical data which demonstrated an overall low degree of guideline-adherence in the use of CA in patients with suspected CCS in the German health care setting. To improve adherence rates, the availability of and access to non-invasive image guided testing needs to be strengthened. (German Clinical Trials Registry DRKS00015638 - Registration Date: 19.02.2019).

Safety, usability, and performance of a wireless left atrial pressure monitoring system in patients with heart failure: the VECTOR-HF trial.

AIMS: In heart failure (HF), implantable haemodynamic monitoring devices have been shown to optimize therapy, anticipating clinical decompensation and preventing hospitalization. Direct left-sided haemodynamic sensors offer theoretical benefits beyond pulmonary artery pressure monitoring systems. We evaluated the safety, usability, and performance of a novel left atrial pressure (LAP) monitoring system in HF patients. METHODS AND RESULTS: The VECTOR-HF study (NCT03775161) was a first-in-human, prospective, multicentre, single-arm, clinical trial enrolling 30 patients with HF. The device consisted of an interatrial positioned leadless sensor, able to transmit LAP data wirelessly. After 3 months, a right heart catheterization was performed to correlate mean pulmonary capillary wedge pressure (PCWP) with simultaneous mean LAP obtained from the device. Remote LAP measurements were then used to guide patient management. The miniaturized device was successfully implanted in all 30 patients, without acute major adverse cardiac and neurological events (MACNE). At 3 months, freedom from short-term MACNE was 97%. Agreement between sensor-calculated LAP and PCWP was consistent, with a mean difference of -0.22 ± 4.92 mmHg, the correlation coefficient and the Lin's concordance correlation coefficient values were equal to 0.79 (p < 0.0001) and 0.776 (95% confidence interval 0.582-0.886), respectively. Preliminary experience with V-LAP-based HF management was associated with significant improvements in New York Heart Association (NYHA) functional class (32% of patients reached NYHA class II at 6 months, p < 0.005; 60% of patients at 12 months, p < 0.005) and 6-min walk test distance (from 244.59 ± 119.59 m at baseline to 311.78 ± 129.88 m after 6 months, p < 0.05, and 343.95 ± 146.15 m after 12 months, p < 0.05). CONCLUSION: The V-LAP™ monitoring system proved to be generally safe and provided a good correlation with invasive PCWP. Initial evidence also suggests possible improvement in HF clinical symptoms.

The V-LAP System for Remote Left Atrial Pressure Monitoring of Patients With Heart Failure: Remote Left Atrial Pressure Monitoring.

OBJECTIVE: Patients with heart failure (HF) are at an increased risk of hospital admissions. The aim of this report is to describe the feasibility, safety and accuracy of a novel wireless left atrial pressure (LAP) monitoring system in patients with HF. METHODS: The V-LAP Left Atrium Monitoring systEm for Patients With Chronic sysTOlic & Diastolic Congestive heart Failure (VECTOR-HF) study is a prospective, multicenter, single-arm, open-label, first-in human clinical trial to assess the safety, performance and usability of the V-LAP system (Vectorious Medical Technologies) in patients with New York Heart Association class III HF. The device was implanted in the interatrial septum via a percutaneous, trans-septal approach guided by fluoroscopy and echocardiography. Primary endpoints included the successful deployment of the implant, the ability to perform initial pressure measurements and safety outcomes. RESULTS: To date, 24 patients have received implants of the LAP-monitoring device. No device-related complications have occurred. LAP was reported accurately, agreeing well with wedge pressure at 3 months (Lin concordance correlation coefficient = 0.850). After 6 months, New York Heart Association class improved in 40% of the patients (95% CI = 16.4%-63.5%), while the 6-minute walk test distance had not changed significantly (313.9 ± 144.9 vs 232.5 ± 129.9 meters; P = 0.076). CONCLUSION: The V-LAP left atrium monitoring system appears to be safe and accurate.

Human Skin Permeation Enhancement Using PLGA Nanoparticles Is Mediated by Local pH Changes.

The steady improvement and optimization of transdermal permeation is a constant and challenging pharmaceutical task. In this study the influence of poly(lactide-co-glycolide) (PLGA) nanoparticles on the dermal permeation of the anti-inflammatory drug flufenamic acid (FFA) was investigated. For this aim, different vehicles under non-buffered and buffered conditions and different skin models (human heat separated epidermis and reconstructed human epidermis equivalents) were tested. Permeation experiments were performed using static Franz diffusion cells under infinite dosing conditions. Already the presence of drug-free nanoparticles increased drug permeation across the skin. Drug permeation was even enhanced when applying drug-loaded nanoparticles. In contrast, buffered vehicles with different pH values (pH 5.4-7.4) revealed the influence of the pH on the permeation of FFA. The change of the surrounding pH of the biodegradable nanoparticulate system was demonstrated and visualized using pH-sensitive fluorescent probes. While a potential contribution of hair follicles could be ruled out, our data suggest that the enhanced permeation of FFA through human skin in the presence of PLGA nanoparticles is mediated by a locally decreased pH during hydrolytic degradation of this polymer. This hypothesis is supported by the observation that skin permeation of the weak base caffeine was not affected.

Tofacitinib Loaded Squalenyl Nanoparticles for Targeted Follicular Delivery in Inflammatory Skin Diseases.

Tofacitinib (TFB), a Janus kinase inhibitor, has shown excellent success off-label in treating various dermatological diseases, especially alopecia areata (AA). However, TFB's safe and targeted delivery into hair follicles (HFs) is highly desirable due to its systemic adverse effects. Nanoparticles (NPs) can enhance targeted follicular drug delivery and minimize interfollicular permeation and thereby reduce systemic drug exposure. In this study, we report a facile method to assemble the stable and uniform 240 nm TFB loaded squalenyl derivative (SqD) nanoparticles (TFB SqD NPs) in aqueous solution, which allowed an excellent loading capacity (LC) of 20%. The SqD NPs showed an enhanced TFB delivery into HFs compared to the aqueous formulations of plain drug in an ex vivo pig ear model. Furthermore, the therapeutic efficacy of the TFB SqD NPs was studied in a mouse model of allergic dermatitis by ear swelling reduction and compared to TFB dissolved in a non-aqueous mixture of acetone and DMSO (7:1 v/v). Whereas such formulation would not be acceptable for use in the clinic, the TFB SqD NPs dispersed in water illustrated a better reduction in inflammatory effects than plain TFB's aqueous formulation, implying both encouraging good in vivo efficacy and safety. These findings support the potential of TFB SqD NPs for developing a long-term topical therapy of AA.

Synthesis and Biopharmaceutical Characterization of Amphiphilic Squalenyl Derivative Based Versatile Drug Delivery Platform.

Limited drug loading capacity (LC), mostly below 5% w/w, is a significant drawback of nanoparticulate drug delivery systems (DDS). Squalenoylation technology, which employs bioconjugation of squalenyl moiety and drug, allows self-assemble of nanoparticles (NPs) in aqueous media with significantly high LC (>30% w/w). The synthesis and particle preparation of squalenoylated prodrugs are, however, not facile for molecules with multiple reactive groups. Taking a different approach, we describe the synthesis of amphiphilic squalenyl derivatives (SqDs) as well as the physicochemical and biopharmaceutical characterizations of their self-assembled NPs as DDSs. The SqDs included in this study are (i) cationic squalenyl diethanolamine (ii) PEGylated SqD (PEG 750 Da), (iii) PEGylated SqD (PEG 3,000 Da), and (iv) anionic squalenyl hydrogen sulfate. All four SqDs self-assemble into NPs in a size range from 100 to 200 nm in an aqueous solution. Furthermore, all NP derivatives demonstrate appropriate biocompatibility and adequate colloidal stability in physiological relevant pH environments. The mucoprotein binding of PEGylated NPs is reduced compared to the charged NPs. Most importantly, this technology allows excellent LC (at maximum of 45% w/w) of a wide range of multifunctional compounds, varying in physicochemical properties and molecular weight. Interestingly, the drug release profile can be tuned by different loading methods. In summary, the SqD-based NPs appear as versatile drug delivery platforms.

Transcatheter aortic valve implantation versus surgical aortic valve replacement in low-risk patients: a propensity score-matched analysis.

OBJECTIVES: The aim of the study was to determine the differences in outcomes of surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) in low-risk patients. METHODS: All patients with a logistic EuroSCORE II <4% who underwent transfemoral TAVI between 2008 and 2016 (n = 955) or SAVR between 2009 and 2014 (n = 886) at our centre were included. One hundred and nine patients per group were available for propensity score matching. RESULTS: Mortality during the 30-day follow-up showed no differences (SAVR vs TAVI: 1.1% vs 1.8%, P = 1.0) but the rates of permanent pacemaker implantation (0.0 vs 14.8%, P < 0.001) and paravalvular leakage ≥ moderate (0.0 vs 7.0%, P = 0.017) were higher in TAVI patients. No difference was found regarding postoperative effective orifice area and transvalvular pressure gradients. Although, the 1-year survival was similar between both groups; 3- and 5-year survival was significantly inferior in the TAVI patient cohort. CONCLUSIONS: TAVI yielded similar short-term outcomes compared with SAVR despite higher rates of permanent pacemaker implantation and paravalvular leakage ≥ moderate, but inferior long-term survival. Poorer long-term outcomes of the TAVI patient cohort were attributable to a more comorbid TAVI population. This emphasizes the need for long-term results from randomized controlled trials before TAVI can be broadly expanded to younger low-risk patients.

Mitral regurgitation severity predicts one-year therapeutic benefit of Tendyne transcatheter mitral valve implantation.

AIMS: Longitudinal outcomes of transcatheter therapies for secondary mitral regurgitation (MR) have been variable. This study examined predictors of one-year outcome following transcatheter mitral valve implantation (TMVI) with the Tendyne device. METHODS AND RESULTS: The first 100 consecutive patients with moderate-severe or severe MR enrolled in the Tendyne CE Mark trial were examined. Multivariable analyses assessed the impact of preoperative clinical and echocardiographic characteristics on one-year freedom from death or heart failure hospitalisation (HFH). All 100 patients underwent Tendyne TMVI without operative mortality. Univariate analysis was performed on implanted subjects, followed by multivariate analysis in those with complete predictive variable data. Patient characteristics: 76.5% male, 60.8% NYHA Class III/IV, age 75.6±7.5 years and Society of Thoracic Surgeons predicted risk of mortality of 8.5±6.1%. Increased left ventricular end-diastolic dimension was associated with one-year Tendyne benefit following univariate analysis (OR 0.35, p=0.010). Following multivariable adjustment, only severe MR, defined as a composite of effective regurgitant orifice area ≥0.3 cm2 or regurgitant volume ≥45 ml, was associated with freedom from death or HFH at one year (OR 0.16, p=0.032). CONCLUSIONS: Preoperative severe MR was predictive of improved one-year outcome following Tendyne TMVI. These results may inform therapy selection for the management of secondary MR and left ventricular dilatation.

1-Year Outcomes of the CENTERA-EU Trial Assessing a Novel Self-Expanding Transcatheter Heart Valve.

OBJECTIVES: The purpose of this study is to report the 1-year results of the CENTERA-EU trial. BACKGROUND: The CENTERA transcatheter heart valve (THV) (Edwards Lifesciences, Irvine, California) is a low-profile (14-F eSheath compatible), self-expanding nitinol valve, with a motorized delivery system allowing for repositionability. The 30-day results of the CENTERA-EU trial demonstrated the short-term safety and effectiveness of the valve. METHODS: Implantations were completed in 23 centers in Europe, Australia, and New Zealand. Transfemoral access was used in all patients. Echocardiographic outcomes were adjudicated by a core laboratory at baseline, discharge, 30 days, 6 months, and 1 year. Major adverse clinical events were adjudicated by an independent clinical events committee. RESULTS: Between March 2015 and July 2016, 203 high-risk patients (age 82.7 ± 5.5 years, 67.5% women, 68.0% New York Heart Association functional class III or IV, Society of Thoracic Surgeons score 6.1 ± 4.2%) with severe, symptomatic aortic stenosis underwent transcatheter aortic valve replacement with the CENTERA THV. The primary endpoint of the study was 30-day mortality (1.0%). At 1 year, overall mortality was 9.1%, cardiovascular mortality was 4.6%, disabling stroke was 4.1%, new permanent pacemakers were implanted in 6.5% of patients at risk, and cardiac-related rehospitalization was 6.8%. Hemodynamic parameters were stable at 1 year, with a mean aortic valve gradient of 8.1 ± 4.7 mm Hg, a mean effective orifice area of 1.7 ± 0.42 cm2, and no incidences of severe or moderate aortic regurgitation. CONCLUSIONS: The CENTERA-EU trial demonstrated mid-term safety and effectiveness of the CENTERA THV, with low mortality, sustained improvements in hemodynamic performances, and low incidence of permanent pacemaker implantations in high-risk patients with symptomatic aortic stenosis. (Safety and Performance of the Edwards CENTERA-EU Self-Expanding Transcatheter Heart Valve [CENTERA-2]; NCT02458560).

Can We Predict Failure of Mitral Valve Repair?

OBJECTIVE: To identify echocardiographic and surgical risk factors for failure after mitral valve repair. METHODS: We identified a total of 77 consecutive patients from our institutional mitral valve surgery database who required redo mitral valve surgery due to recurrence of mitral regurgitation after primary mitral valve repair. A control group of 138 patients who had a stable echocardiographic long-term result was included based on propensity score matching. Systematic analysis of echocardiographic parameters was performed before primary surgery; after mitral valve repair and prior to redo surgery. Risk factor analysis was performed using multivariate Cox regression model. RESULTS: Redo surgery was associated with the presence of pulmonary hypertension ≥ 50 mmHg (p = 0.02), a mean transmitral gradient > 5 mmHg (p = 0.001), left ventricular ejection fraction ≤ 45% (p = 0.05) before surgery and mitral regurgitation ≥moderate at time of discharge (p = 0.002) in the whole cohort. Patients with functional mitral valve regurgitation had a higher tendency to undergo redo surgery if preoperative left ventricular end-diastolic diameter exceeded 65 mm (p = 0.043) and if postoperative tenting height exceeded 6 mm (p = 0.018). Low ejection fraction was not significantly associated with the need for redo mitral valve surgery in the functional subgroup. CONCLUSIONS: Recurrent mitral regurgitation is still a valuable problem and is associated with relevant perioperative mortality. Patients with severe mitral regurgitation should undergo early mitral valve repair surgery as long as systolic pulmonary artery pressure is low, left ventricular ejection fraction is preserved, and LVEED is deceeds 65 mm.

Risk factors to identify patients who may not benefit from whole brain irradiation for brain metastases - a single institution analysis.

BACKGROUND: Radiotherapy plays a major role in the management of brain metastases. This study aimed to identify the subset of patients with multiple brain metastases who may not benefit from whole brain irradiation (WBI) due to a short survival time regardless of treatment. METHODS: We analyzed a total of 339 patient records with brain metastases treated with whole brain radiotherapy from January 2009 to January 2016. External beam radiotherapy techniques were used to deliver 33 Gy in 11 fractions (4 fractions per week) to the whole brain. Eight clinical factors with a potential influence on survival were investigated using the Kaplan-Meier method. All factors with a P < 0.05 in univariate analysis were entered into multivariate analysis using Cox regression. RESULTS: In the present series of 339 patients, median survival time was 2.5 months (M; range, 0-61 months). Four risk factors Karnofsky Performance Score (KPS) < 70, age > 70, > 3 of metastases intracranial, uncontrolled primary tumor) were identified that were significant and negatively correlated with median survival time. Patients with no risk factors had a median survival of 4.7 M; one risk factor, 2.5 M; two risk factors, 2.3 M; and 3-4 risk factors, 0.4 M (p < 0.00001). CONCLUSIONS: Patients with identified risk factors might have a negatively impacted overall survival after WBI. Accordingly, patients who will not benefit from WBI can be easily predicted if they have 3-4 of these risk factors.

Transcatheter Mitral Valve Replacement in Patients With Previous Aortic Valve Replacement.

BACKGROUND: Transcatheter mitral valve replacement (TMVR) may mature to become a therapeutic option for high-risk patients with severe mitral regurgitation (MR), particularly in patients at high or prohibitive surgical risk. MR patients with preexisting aortic valve prosthesis have been excluded from most TMVR trials because of the potential risks of left ventricular outflow tract obstruction or interaction between the TMVR anchoring mechanism and the aortic prosthesis. We describe the procedural and short-term outcomes of transapical TMVR with the Tiara valve in patients experiencing severe symptomatic MR with previous aortic valve replacement (AVR). METHODS AND RESULTS: Twelve consecutive high surgical risk patients (11 men; mean age, 75±6 years) with aortic valve prosthesis and severe MR underwent TMVR with Tiara valve. Aortic valves were mechanical in 5 and biological in 7 patients, while 1 patient had previously undergone implantation of a transcatheter valve within a failed bioprosthetic surgical valve. Six patients (50%) had undergone redo surgical aortic valve replacement. Clinical characteristics of the group include prior mitral valve repair in 2, prior coronary bypass grafting surgery in 5, chronic atrial fibrillation in 7, renal failure in 9, and pacemaker/cardiac resynchronization device in 9 patients. Mean Society of Thoracic Surgery score and EuroSCORE II were 10.5±4.4 and 12.4±3.7, respectively. Mean baseline left ventricular ejection fraction was 35.5±5.3% (range, 30%-45%). The Tiara valve was implanted uneventfully in all patients. Device migration or left ventricular outflow tract obstruction was not observed. No patient required conversion to open heart surgery or periprocedural hemodynamic support. Procedural success was 100% with no death, MI, stroke, major bleeding, or access site complications at 30 days. MR was eliminated in all 12 patients immediately after implantation. CONCLUSIONS: Transapical mitral valve replacement with the Tiara valve in high-risk patients with severe MR and aortic valve prostheses is technically feasible and can be performed safely.

Updated strategies in the treatment of benign diseases-a patterns of care study of the german cooperative group on benign diseases.

PURPOSE: Radiation therapy (RT) is a common treatment for benign diseases in Germany. Because the treatment concepts are inconsistent, we conducted this pattern-of-care study on behalf of the German Cooperative Group on Benign Diseases to evaluate treatment standards in Germany. METHODS AND MATERIALS: Questionnaires were mailed to all radiation therapy facilities in Germany. We assessed the treatment equipment, annual number of patients, treatment indications, and, in particular, treatment strategies in patients with benign diseases in 2014. RESULTS: We evaluated questionnaires returned by 116 participating institutions, of which 41 were ambulatory health care centers, 28 were private institutions, 27 were community hospitals, and 20 were university hospitals. On average, 2 linac accelerators and 2 megavoltage units were available in each institution. In 2014, a total of 36,830 patients were treated for benign diseases: 16,989 for degenerative diseases (peritendinitis humeroscapularis n = 2691; epicondylitis humeri n = 3788; heel spur n = 10,510); 14,936 for osteoarthritis (coxarthrosis n = 2230; gonarthrosis n = 2623; omarthrosis n = 2691; rhizarthrosis n = 2440; polyarthrosis n = 2297; others n = 2655); 1563 for hyperproliferative diseases (morbus Dupuytren n = 960; morbus Ledderhose n = 441; keloids n = 139; pterygium of the conjunctiva n = 3; other hyperproliferative diseases n = 20); 2440 for functional disorders (gynecomastia n = 843; Graves' disease n = 205; lymphatic fistula n = 178; heterotopic ossification prophylaxis n = 1214); 859 for stereotactic RT in the central nervous system (arteriovenous malformation n = 53; meningioma n = 425; acoustic neuroma n = 201; pituitary adenoma n = 131; others n = 49), and 43 for rare indications (pigmented villonodular synovitis n = 20 or vertebral hemangioma n = 23). The mean whole dose was <10 Gy in the treatment of degenerative disorders, 25 Gy for hyperproliferative diseases, 15 Gy for functional disorders, and <50 Gy for stereotactic RT. CONCLUSIONS: In 2014, RT had an important role in the treatment of benign diseases. Because treatment concepts are inherent, we recommend treatment based on the guidelines written by the German Cooperative Group on Benign Diseases.

Radiotherapy for calcaneodynia, achillodynia, painful gonarthrosis, bursitis trochanterica, and painful shoulder syndrome - Early and late results of a prospective clinical quality assessment.

BACKGROUND: The aim of this prospective clinical quality assessment was to evaluate the short-term and long-term efficacy of low dose radiotherapy (RT) for calcaneodynia, achillodynia, painful gonarthrosis, painful bursitis trochanterica, and painful shoulder syndrome. METHODS: Between October 2011 and October 2013, patients with calcaneodynia, achillodynia, painful gonarthrosis, painful bursitis trochanterica, and painful shoulder syndrome were recruited for this prospective clinical quality assessment. Single doses of 0.5-1.0 Gy and a total dose of 6.0 Gy per series were used. Pain was measured before and directly after RT (early response) with a visual analogue scale (VAS). Additionally, pain relief was measured with the four-scale pain score according to "von Pannewitz" (VPS) immediately at the end of RT and during follow-up. Within this context we defined a good response as complete pain relief and markedly improved. The assessment of the long-term efficacy was carried out by a telephone survey. RESULTS: 703 evaluable patients (461 female, 242 male) with a mean age of 63.2 years (28-96) were recruited for this prospective clinical quality assessment. In 254 patients RT was performed with the linear accelerator, 449 patients received orthovoltage radiotherapy. After a median follow-up of 33 months (3-60) 437 patients could be reached for evaluation of follow up results. The mean VAS value before treatment was 6.63 (1.9-10) and immediately on completion of RT 4.51 (0-10) (p < 0,001). Concerning the VPS immediately on completion of RT, a good response could be achieved in 264/703 patients (37.6%), and with the follow up in 255/437 patients (58.4%) (p < 0.001). Only in patients with gonarthrosis we could not observe a significantly improved long-term success in comparison to the results immediately after RT (30.2% versus 29.9%). CONCLUSION: Low dose RT is a very effective treatment for the management of calcaneodynia, achillodynia, painful gonarthrosis, painful bursitis trochanterica, and painful shoulder syndrome. Due to the delayed onset of analgesic effects low dose RT results in a significantly improved long-term efficacy in comparison to the results immediately after RT particularly in patients with calcaneodynia, achillodynia, bursitis trochanterica, and shoulder syndrome.

Prospective multicentre evaluation of a novel, low-profile transapical delivery system for self-expandable transcatheter aortic valve implantation: 6-month outcomes.

OBJECTIVES: We assessed the safety and efficacy of a novel low-profile, 22-Fr transapical delivery system together with the ACURATE neo™ resheathable transcatheter heart valve. METHODS: This prospective, single-arm, multicentre study enrolled 60 patients with severe symptomatic aortic stenosis and high surgical risk ineligible for transfemoral access. Primary end points were 6-month mortality and procedural success. RESULTS: The mean age of patients was 79.8 ± 4.7 years, and the patients had severe comorbidities including coronary artery disease (71.7%), diabetes (38.3%), atrial fibrillation (30.0%) and chronic obstructive pulmonary disease (21.7%); logistic EuroSCORE-I, -II and the Society of Thoracic Surgeons (STS) scores were 20.9 ± 8.9%, 6.1 ± 5.0% and 4.3 ± 2.9%, respectively. A non-rib spreading approach using soft tissue retractors only was used in 88.3% of patients (n = 53). Resheathing and repositioning of transcatheter heart valve were performed in 6.7% of cases (n = 4); the device implantation time was 3 ± 2 min. Apical access site complications occurred in 1.7% (n = 1). Procedural success was 98.3% (n = 59), and procedural success in the absence of major adverse cardiac and cerebrovascular events at 30 days was 90.0% (n = 54). At 30 days, cardiovascular and overall mortality were 8.3% (n = 5), stroke rate was 1.7% (n = 1), and 17.2% of patients (n = 10) received a permanent pacemaker implant. No paravalvular leakage ≥2+ was observed, and the mean transvalvular gradient was 5.9 ± 2.7 mmHg. At 6 months, survival was 84.3% with sustained haemodynamic results. CONCLUSIONS: This study indicates safety and efficacy of transapical aortic valve implantation using a novel low-profile delivery system. High procedural success, short implantation times and a low rate of apical access site complications underline the favourable safety profile and ease of use. Clinical trial registration: ClinicalTrials.gov: NCT02950428.

Transcatheter Tricuspid Valve-In-Ring and Aortic Valve-In-Valve Implantation.

Background Transcatheter heart valve (THV) therapies have shown to be an alternative to surgical valve replacement, especially in high-risk patients requiring redo surgery. However, reports of transcatheter-based interventions in tricuspid valve position are scarce. Case Description Here, we report a case of successful concomitant transcatheter aortic valve-in-valve (ViV) and tricuspid valve-in-ring (ViR) procedures using a 23-mm CoreValve Evolut R THV (Medtronic, Inc., Minneapolis, Minnesota, United States) in aortic position and a 29-mm SAPIEN3 (Edwards Lifesciences, Inc., Irvine, California, United States) THV in tricuspid position. Conclusion This case demonstrates feasibility of concomitant transcatheter aortic ViV and tricuspid ViR procedures.

Short-Term Outcome and Hemodynamic Performance of Next-Generation Self-Expanding Versus Balloon-Expandable Transcatheter Aortic Valves in Patients With Small Aortic Annulus: A Multicenter Propensity-Matched Comparison.

BACKGROUND: Surgical aortic valve replacement in patients with small annular dimensions is challenging because they are at increased risk for prosthesis-patient mismatch and impaired outcomes. Transcatheter aortic valve replacement might be a good alternative; however, comparative data on different transcatheter heart valves are missing. METHODS AND RESULTS: This multicenter, propensity score-matched study compared hemodynamics and early clinical outcomes in 246 patients with an aortic annulus area <400 mm2 undergoing transcatheter aortic valve replacement with either a self-expanding transcatheter heart valve (Symetis ACURATE neo, n=129) or a balloon-expandable transcatheter heart valve (Edwards SAPIEN 3, n=117). The 1:1 propensity score matching resulted in 92 matched pairs. For ACURATE neo versus SAPIEN 3-treated patients, 30-day mortality (0.0% versus 1.0%), 1-year mortality (8.3% versus 13.3%), incidence of stroke (3.3% versus 2.2%), life-threatening bleeding (1.1% versus 1.1%), and major vascular complications (2.2% versus 6.5%), as well as pacemaker implantation rate (12.0% versus 15.2%), were similar. Paravalvular regurgitation ≥moderate was rare in both groups (4.5% versus 3.6%). The ACURATE neo presented lower mean transvalvular gradients (9.3 versus 14.5 mm Hg; P<0.001), larger indexed effective orifice areas (0.96 versus 0.80 cm2/m2; P=0.003), and lower rates of severe prosthesis-patient mismatch (3% versus 22%; P=0.004). Hemodynamics were sustained at 1-year follow-up. CONCLUSIONS: Albeit a similar safety profile with low clinical event rates, transcatheter aortic valve replacement with the ACURATE neo valve resulted in lower transvalvular gradients and consequently less prosthesis-patient mismatch compared with the SAPIEN 3 in patients with small annulus. These results emphasize the need of careful prosthesis selection in each individual patient.