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BACKGROUND: Bicuspid aortic valve (BAV) affects approximately 1.5% of the general population and is seen in nearly 50% of candidates for aortic valve replacement (AVR). Despite increasingly utilised transcatheter aortic valve implantation (TAVI) in aortic stenosis (AS) patients, its use among patients with severe bicuspid AS is limited as BAV is a heterogeneous disease associated with multiple and complex anatomical challenges.AIM: To investigate the one-year outcomes of TAVI using the balloon-expandable Myval transcatheter heart valve (THV) (Meril Life Sciences Pvt. Ltd., Vapi, India) in patients with severe bicuspid AS.METHODS AND RESULTS: We collected data from consecutive patients with bicuspid AS who underwent TAVI with the Myval THV and had at least one-year follow-up. Baseline characteristics, procedural, and 30-day echocardiographic and clinical outcomes were collected. Sixty-two patients were included in the study. The median age was 72 [66.3, 77.0] years, 45 (72.6%) were males, and the mean STS PROM score was 3.2 ± 2.2%. All TAVI procedures were performed via the transfemoral route. The median follow-up duration was 13.5 [12.2, 18.3] months; all-cause mortality was reported in 7 (11.3%) patients and cardiovascular hospitalisation in 6 (10.6%) patients. All-stroke was reported in 2 (3.2%), permanent pacemaker implantation 5 (8.3%), and myocardial infarction 1 (1.6%) patients. The echocardiographic assessment revealed a mean pressure gradient of 10 [8, 16.5] mmHg, effective orifice area 1.7 [1.4, 1.9] cm2, moderate AR in 1 (2%), mild AR in 14 (27%), and none/trace AR in 37 (71%). In total, 1 patient was diagnosed with valve thrombosis (2.1%), Stage II (moderate) haemodynamic deterioration was seen in 3 (6.4%), and stage III (severe) haemodynamic deterioration in 1 (2.1%) patient.CONCLUSIONS: TAVI with the Myval THV in selected BAV anatomy is associated with favourable one-year hemodynamic and clinical outcomes.

Objectives No consensus exists upon whether arterial and venous blood samples are equivalent when it comes to coagulation analyses. We therefore conducted a comparative cohort study to clarify if arteriovenous differences affect analyses of primary and secondary hemostasis as well as fibrinolysis. Methods Simultaneous paired blood samplings were obtained from a cannula in the radial artery and an antecubital venipuncture in 100 patients immediately before or one day after thoracic surgery. Analyses of platelet count and aggregation, International Normalized Ratio (INR), activated partial thromboplastin time (APTT), antithrombin, thrombin time, fibrinogen, D-dimer, rotational thromboelastometry (ROTEM), thrombin generation, prothrombin fragment 1 + 2, and an in-house dynamic fibrin clot formation and lysis assay were performed. Results No differences were found between arterial and venous samples for the far majority of parameters. The only differences were found in INR, median (IQR): venous, 1.1 (0.2) vs. arterial, 1.1 (0.2) (p Conclusions The sampling site does not affect the majority of coagulation analyses. Small differences were found for two parameters. Due to numerically very discrete differences, they are of no clinical relevance. In conclusion, the present data suggest that both samples obtained from arterial and venous blood may be applied for analyses of coagulation and fibrinolysis.

Aims The aims of the study were to compare clinical outcomes and valve durability after 8 years of follow-up in patients with symptomatic severe aortic valve stenosis at low surgical risk treated with either transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR). Methods and results In the NOTION trial, patients with symptomatic severe aortic valve stenosis were randomized to TAVI or SAVR. Clinical status, echocardiography, structural valve deterioration, and failure were assessed using standardized definitions. In total, 280 patients were randomized to TAVI (n = 145) or SAVR (n = 135). Baseline characteristics were similar, including mean age of 79.1 ± 4.8 years and a mean STS score of 3.0 ± 1.7%. At 8-year follow-up, the estimated risk of the composite outcome of all-cause mortality, stroke, or myocardial infarction was 54.5% after TAVI and 54.8% after SAVR (P = 0.94). The estimated risks for all-cause mortality (51.8% vs. 52.6%; P = 0.90), stroke (8.3% vs. 9.1%; P = 0.90), or myocardial infarction (6.2% vs. 3.8%; P = 0.33) were similar after TAVI and SAVR. The risk of structural valve deterioration was lower after TAVI than after SAVR (13.9% vs. 28.3%; P = 0.0017), whereas the risk of bioprosthetic valve failure was similar (8.7% vs. 10.5%; P = 0.61). Conclusions In patients with severe aortic valve stenosis at low surgical risk randomized to TAVI or SAVR, there were no significant differences in the risk for all-cause mortality, stroke, or myocardial infarction, as well as the risk of bioprosthetic valve failure after 8 years of follow-up. Clinical trial registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01057173., Graphical Abstract Clinical and aortic bioprosthetic valve failure 8 years after transcatheter and surgical aortic valve replacement. CI, confidence interval; HR, hazard ratio.

Background Permanent pacemaker implantation (PPI) remains one of the main drawbacks of transcatheter aortic valve replacement (TAVR), but scarce data exist on PPI after valve-in-valve (ViV) TAVR, particularly with the use of newer-generation transcatheter heart valves (THVs). Objectives The goal of this study was to determine the incidence, factors associated with, and clinical impact of PPI in a large series of ViV-TAVR procedures. Methods Data were obtained from the multicenter VIVID Registry and included the main baseline and procedural characteristics, in-hospital and late (median follow-up: 13 months [interquartile range: 3 to 41 months]) outcomes analyzed according to the need of periprocedural PPI. All THVs except CoreValve, Cribier-Edwards, Sapien, and Sapien XT were considered to be new-generation THVs. Results A total of 1,987 patients without prior PPI undergoing ViV-TAVR from 2007 to 2020 were included. Of these, 128 patients (6.4%) had PPI after TAVR, with a significant decrease in the incidence of PPI with the use of new-generation THVs (4.7% vs. 7.4%; p = 0.017), mainly related to a reduced PPI rate with the Evolut R/Pro versus CoreValve (3.7% vs. 9.0%; p = 0.002). There were no significant differences in PPI rates between newer-generation balloon- and self-expanding THVs (6.1% vs. 3.9%; p = 0.18). In the multivariable analysis, older age (odds ratio [OR]: 1.05 for each increase of 1 year; 95% confidence interval [CI]: 1.02 to 1.07; p = 0.001), larger THV size (OR: 1.10; 95% CI: 1.01 to 1.20; p = 0.02), and previous right bundle branch block (OR: 2.04; 95% CI: 1.00 to 4.17; p = 0.05) were associated with an increased risk of PPI. There were no differences in 30-day mortality between the PPI (4.7%) and no-PPI (2.7%) groups (p = 0.19), but PPI patients exhibited a trend toward higher mortality risk at follow-up (hazard ratio: 1.39; 95% CI: 1.02 to 1.91; p = 0.04; p = 0.08 after adjusting for age differences between groups). Conclusions In a contemporary large series of ViV-TAVR patients, the rate of periprocedural PPI was relatively low, and its incidence decreased with the use of new-generation THV systems. PPI following ViV-TAVR was associated with a trend toward increased mortality at follow-up.

Bicuspid aortic valve (BAV) is the most common valvular congenital anomaly and is apparent in nearly 50% of candidates for AV replacement. While transcatheter aortic valve implantation (TAVI) is a recommended treatment for patients with symptomatic severe aortic stenosis (AS) at all surgical risk levels, experience with TAVI in severe bicuspid AS is limited. TAVI in BAV is still a challenge due to its association with multiple and complex anatomical considerations. A retrospective study has been conducted to investigate TAVI’s procedural and 30-day outcomes using the Myval transcatheter heart valve (THV) (Meril Life Sciences Pvt. Ltd. Vapi, Gujarat, India) in patients with severe bicuspid AS. Data were collected on 68 patients with severe bicuspid AS who underwent TAVI with the Myval THV. Baseline characteristics, procedural, 30-day echocardiographic and clinical outcomes were collected. The mean age and STS PROM score were 72.6 ± 9.4 and 3.54 ± 2.1. Procedures were performed via the transfemoral route in 98.5%. Major vascular complications (1.5%) and life-threatening bleeding (1.5%) occurred infrequently. No patient had coronary obstruction, second valve implantation or conversion to surgery. On 30-day echocardiography, the mean transvalvular gradient and effective orifice area were 9.8 ± 4.5 mmHg and 1.8 ± 0.4 cm2, respectively. None/trace aortic regurgitation occurred in 76.5%, mild AR in 20.5% and moderate AR in 3%. The permanent pacemaker implantation rate was 8.5% and 30-day all-cause death occurred in 3.0% of cases. TAVI with the Myval THV in selected BAV anatomy is associated with favorable short-term hemodynamic and clinical outcomes.

Bolus serves as a tissue equivalent material that shifts the 95-100% isodose line towards the skin and subcutaneous tissue. The need for bolus for all breast cancer patients planned for postmastectomy radiation therapy (PMRT) has been questioned. The work was initiated by the faculty of the European SocieTy for Radiotherapy & Oncology (ESTRO) breast cancer courses and represents a multidisciplinary international breast cancer expert collaboration to optimize PMRT. Due to the lack of randomised trials evaluating the benefits of bolus, we designed a stepwise project to evaluate the existing evidence about the use of bolus in the setting of PMRT to achieve an international consensus for the indications of bolus in PMRT, based on the Delphi method. (c) 2021 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 164 (2021) 115-121

Highlights • We establish selection criteria for the randomised DBCG Proton Trial. • DBCG proton selection criteria: mean heart dose ≥ 4 Gy and/or lung V17Gy/V20Gy ≥ 37%. • ~1 in 5 patients undergoing loco-regional radiotherapy will be eligible for the trial., Background and purpose Adjuvant radiotherapy of internal mammary nodes (IMN) improves survival in high-risk early breast cancer patients but inevitably leads to more dose to heart and lung. Target coverage is often compromised to meet heart/lung dose constraints. We estimate heart and lung dose when target coverage is not compromised in consecutive patients. These estimates are used to guide the choice of selection criteria for the randomised Danish Breast Cancer Group (DBCG) Proton Trial. Materials and methods 179 breast cancer patients already treated with loco-regional IMN radiotherapy from 18 European departments were included. If the clinically delivered treatment plan did not comply with defined target coverage requirements, the plan was modified retrospectively until sufficient coverage was reached. The choice of selection criteria was based on the estimated number of eligible patients for different heart and lung dose thresholds in combination with proton therapy capacity limitations and dose–response relationships for heart and lung. Results Median mean heart dose was 3.0 Gy (range, 1.1–8.2 Gy) for left-sided and 1.4 Gy (0.4–11.5 Gy) for right-sided treatment plans. Median V17Gy/V20Gy (hypofractionated/normofractionated plans) for ipsilateral lung was 31% (9–57%). The DBCG Radiotherapy Committee chose mean heart dose ≥ 4 Gy and/or lung V17Gy/V20Gy ≥ 37% as thresholds for inclusion in the randomised trial. Using these thresholds, we estimate that 22% of patients requiring loco-regional IMN radiotherapy will be eligible for the trial. Conclusion The patient selection criteria for the DBCG Proton Trial are mean heart dose ≥ 4 Gy and/or lung V17Gy/V20Gy ≥ 37%.

Aims: To evaluate how common radiation therapy techniques perform in the setting of the new European Society for Radiotherapy and Oncology-Advisory Committee in Radiation Oncology Practice (ESTRO-ACROP) delineation recommendations for immediate breast reconstruction (IBR). Materials and methods: Seven Danish radiation therapy centres and six international European centres participated in this project. Two breast cancer cases (one left-sided and one right-sided) with a retropectoral implant were chosen for radiation therapy planning using deep-inspiration breath-hold. Target volumes were delineated according to ESTRO-ACROP delineation recommendations. The centres were asked to plan the cases using any radiation therapy technique according to the Danish Breast Cancer Group plan objectives. Results: In total, 35 treatment plans were collected. Half of the submitted plans, for both the left-sided and the right-sided case, used the field-in-field (FiF) technique (nine for each), a quarter used volumetric arc radiation therapy (VMAT; five for right-sided, four for left-sided) and the remaining quarter was a mix of inverse intensity-modulated radiation therapy (IMRT), helicoidal therapy and hybrid (combined open fields and VMAT) techniques. Mean clinical target volume doses were in the range 99-102% of the prescribed dose. The median FiF mean heart dose (MHD) for right-sided radiation therapy was 1 Gy (range 0.8-3.7) and 5.2 Gy for left-sided radiation therapy (range 2.2-6.5). For right-sided radiation therapy, the median VMAT MHD was 3.42 Gy, for IMRT was 2.3 Gy and for helicoidal therapy was 5.1 Gy. For left-sided radiation therapy, the median VMAT MHD was 6.3 Gy, for IMRT was 7.8 Gy and for helicoidal therapy was 7.3 Gy. Conclusions: Different radiation therapy techniques could be used to plan radiation therapy in the setting of IBR. FiF provided good coverage with acceptable organ at risk doses. The best dose distribution results as a trade-off between the objectives of target volume coverage and high-dose organ at risk inclusion. The radiation therapy technique affects the interplay between these objectives. (C) 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Aims Due to bioprosthetic valve degeneration, aortic valve-in-valve (ViV) procedures are increasingly performed. There are no data on long-term outcomes after aortic ViV. Our aim was to perform a large-scale assessment of long-term survival and reintervention after aortic ViV. Methods and results A total of 1006 aortic ViV procedures performed more than 5 years ago [mean age 77.7 ± 9.7 years; 58.8% male; median STS-PROM score 7.3% (4.2–12.0)] were included in the analysis. Patients were treated with Medtronic self-expandable valves (CoreValve/Evolut, Medtronic Inc., Minneapolis, MN, USA) (n = 523, 52.0%), Edwards balloon-expandable valves (EBEV, SAPIEN/SAPIEN XT/SAPIEN 3, Edwards Lifesciences, Irvine, CA, USA) (n = 435, 43.2%), and other devices (n = 48, 4.8%). Survival was lower at 8 years in patients with small-failed bioprostheses [internal diameter (ID) ≤ 20 mm] compared with those with large-failed bioprostheses (ID > 20 mm) (33.2% vs. 40.5%, P = 0.01). Independent correlates for mortality included smaller-failed bioprosthetic valves [hazard ratio (HR) 1.07 (95% confidence interval (CI) 1.02–1.13)], age [HR 1.21 (95% CI 1.01–1.45)], and non-transfemoral access [HR 1.43 (95% CI 1.11–1.84)]. There were 40 reinterventions after ViV. Independent correlates for all-cause reintervention included pre-existing severe prosthesis–patient mismatch [subhazard ratio (SHR) 4.34 (95% CI 1.31–14.39)], device malposition [SHR 3.75 (95% CI 1.36–10.35)], EBEV [SHR 3.34 (95% CI 1.26–8.85)], and age [SHR 0.59 (95% CI 0.44–0.78)]. Conclusions The size of the original failed valve may influence long-term mortality, and the type of the transcatheter valve may influence the need for reintervention after aortic ViV.

Background Ultrasound elastography is increasingly available in clinical practice. Recent studies showed higher velocity stiffness in testicular tumors compared to normal testicles. Purpose To evaluate ultrasound elastography in combination with the apparent diffusion coefficient measurements in diffusion weighted (DW) magnetic resonance imaging (MRI) in testicles. DW can be a useful tool in evaluating testicular malignancies. However, the relationship between velocity stiffness and MRI diffusion is not well established. Material and Methods We prospectively included 132 patients with testicular microlithiasis (n = 53), or normal testicular tissue (n = 53), or suspected for testicular cancer (n = 26). All 132 patients underwent ultrasonography including shear wave elastography and MRI diffusion coefficient examination of the scrotum. Results No clinically relevant difference in velocity stiffness was found between normal and testicles with microlithiasis. There was a significant difference in stiffness between patients with testicular microlithiasis (0.78 m/s), normal testicular tissue (0.77 m/s), and patients with testicular cancer (1.95 m/s) ( P ≤ 0.001). Similarly, there was a statistically significant difference in MRI diffusion values between patients with testicular microlithiasis (0.978 × 10−3 mm2 s−1), normal testicular tissue (0.929 × 10−3 mm2 s−1), and testicular cancers (0.743 × 10−3 mm2 s−1) ( P Conclusion Patients with testicular microlithiasis had no malignant characteristics measured with shear wave elastography or MRI diffusion. MRI diffusion and elastography may be useful to preoperatively differentiate benign from malignant testicular lesions.

Aims: The aim of this study was to investigate whether minimising trauma to the aortic annulus and left ventricular outflow tract reduces the occurrence of new conduction disorders and the need for permanent pacemakers. Methods and results: A total of 175 patients (58% female, mean age 83±6 years) underwent transfemoral TAVI with the Boston Scientific ACURATE neo at three centres in Europe. Prosthesis size selection was based on perimeter-derived annular diameter. Predilatation was performed in all with a balloon 1.9±0.9 mm smaller than the perimeter-derived annular diameter. Post-dilatation was performed in 46 (26.3%) with a balloon 1.2±0.9 mm smaller than the perimeter-derived annular diameter. Eighteen patients (10.3%) developed a new left bundle branch block, 13 (7%) a new first-degree AV block, and four (2.3%) received a new permanent pacemaker. Paravalvular regurgitation was none/trace in 66 (37.7%), mild in 101 (57.7%) and moderate in eight (4.6%). At 30 days, the rate of any stroke was 1.7% (3/175), and one patient (0.6%) had died. Conclusions: With careful selection of the balloon and the ACURATE neo prosthesis size, very low rates of new conduction disorders and permanent pacemaker implantation may be achieved without increasing the amount of paravalvular regurgitation.

Purpose Post mastectomy radiation therapy (PMRT) reduces locoregional recurrence (LRR) and breast cancer mortality for selected patients. Bolus overcomes the skin-sparing effect of external-beam radiotherapy, ensuring adequate dose to superficial regions at risk of local recurrence (LR). This systematic review summarizes the current evidence regarding the impact of bolus on LR and acute toxicity in the setting of PMRT. Results 27 studies were included. The use of bolus led to higher rates of acute grade 3 radiation dermatitis (pooled rates of 9.6% with bolus vs. 1.2% without). Pooled crude LR rates from thirteen studies (n = 3756) were similar with (3.5%) and without (3.6%) bolus. Conclusions Bolus may be indicated in cases with a high risk of LR in the skin, but seems not to be necessary for all patients. Further work is needed to define the role of bolus in PMRT.

Ischemic stroke is a feared complication associated with transcatheter aortic valve replacement (TAVR). Data on the late risk of ischemic stroke following TAVR are scarce. This study aimed to investigate the early (0-90 days) and late (90 days-5 years) risk of ischemic cerebrovascular events (CVE) in a large, unselected cohort of patients undergoing TAVR and to compare this risk with a matched background population. Therefore, all patients undergoing first-time TAVR in Denmark were matched to a background population (controls) in a 1:4 ratio based on age, sex, atrial fibrillation (AF), and the major stroke risk factors. A total of 2455 TAVR patients were matched with 9820 controls. TAVR was associated with a significantly higher ischemic CVE risk as compared with their controls in the early phase [hazard ratio (HR) 5.35 [95% CI 3.50-8.17]; p

Quantitative imaging features (radiomics) extracted from apparent diffusion coefficient (ADC) maps of rectal cancer patients can provide additional information to support treatment decision. Most available radiomic computational packages allow extraction of hundreds to thousands of features. However, two major factors can influence the reproducibility of radiomic features: interobserver variability, and imaging filtering applied prior to features extraction. In this exploratory study we seek to determine to what extent various commonly-used features are reproducible with regards to the mentioned factors using ADC maps from two different clinics (56 patients). Features derived from intensity distribution histograms are less sensitive to manual tumour delineation differences, noise in ADC images, pixel size resampling and intensity discretization. Shape features appear to be strongly affected by delineation quality. On the whole, textural features appear to be poorly or moderately reproducible with respect to the image pre-processing perturbations we reproduced.

The Nordic Aortic Valve Intervention (NOTION) was designed to compare transcatheter aortic valve replacement (TAVR) to surgical aortic valve replacement (SAVR) in patients 70 years or older with isolated severe aortic valve stenosis. Clinical and echocardiographic outcomes are presented after 5 years.Patients were enrolled at three Nordic centers and randomized 1:1 to TAVR using the self-expanding CoreValve prosthesis (n=145) or SAVR using any stented bio-prostheses (n=135). The primary composite outcome was the rate of all-cause mortality, stroke, or myocardial infarction at 1 year defined according to Valve Academic Research Consortium-2 criteria.Baseline characteristics were similar. The mean age was 79.1±4.8 years and mean STS-PROM score was 3.0%±1.7%. After 5 years, there were no differences between TAVR and SAVR in the composite outcome (Kaplan-Meier estimates 38.0% vs. 36.3%, log-rank test p=0.86) or any of its components. TAVR patients had larger prosthetic valve area (1.7 cmThese are currently the longest follow-up data comparing TAVR and SAVR in lower risk patients, demonstrating no statistical difference for major clinical outcomes 5 years after TAVR with a self-expanding prosthesis compared to SAVR. Higher rates of prosthetic regurgitation and pacemaker implantation were seen after TAVR.URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01057173.

Background: The NOTION trial (Nordic Aortic Valve Intervention) was designed to compare transcatheter aortic valve replacement (TAVR) with surgical aortic valve replacement (SAVR) in patients ≥70 years old with isolated severe aortic valve stenosis. Clinical and echocardiographic outcomes are presented after 5 years. Methods: Patients were enrolled at 3 Nordic centers and randomized 1:1 to TAVR using the self-expanding CoreValve prosthesis (n=145) or SAVR using any stented bioprostheses (n=135). The primary composite outcome was the rate of all-cause mortality, stroke, or myocardial infarction at 1 year defined according to Valve Academic Research Consortium-2 criteria. Results: Baseline characteristics were similar. The mean age was 79.1±4.8 years and mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 3.0%±1.7%. After 5 years, there were no differences between TAVR and SAVR in the composite outcome (Kaplan-Meier estimates 38.0% versus 36.3%, log-rank test P =0.86) or any of its components. TAVR patients had larger prosthetic valve area (1.7 cm 2 versus 1.2 cm 2 , P P P P Conclusions: These are currently the longest follow-up data comparing TAVR and SAVR in lower risk patients, demonstrating no statistical difference for major clinical outcomes 5 years after TAVR with a self-expanding prosthesis compared to SAVR. Higher rates of prosthetic regurgitation and pacemaker implantation were seen after TAVR. Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT01057173.

Background: Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis and intermediate or high surgical risk. Objectives: The aim of this study was to compare the durability of transcatheter and surgical bioprosthetic aortic valves using standardized criteria. Methods: In the NOTION (Nordic Aortic Valve Intervention) trial, all-comer patients with severe aortic stenosis and lower surgical risk for mortality were randomized 1:1 to TAVR (n = 139) or SAVR (n = 135). Moderate/severe structural valve deterioration (SVD) was defined as a mean gradient ≥20 mm Hg, an increase in mean gradient ≥10 mm Hg from 3 months post-procedure, or more than mild intraprosthetic aortic regurgitation (AR) either new or worsening from 3 months post-procedure. Nonstructural valve deterioration (NSVD) was defined as moderate/severe patient-prosthesis mismatch at 3 months or moderate/severe paravalvular leakage. Bioprosthetic valve failure (BVF) was defined as: valve-related death, aortic valve reintervention, or severe hemodynamic SVD. Results: At 6 years, the rates of all-cause mortality were similar for TAVR (42.5%) and SAVR (37.7%) patients (p = 0.58). The rate of SVD was higher for SAVR than TAVR (24.0% vs. 4.8%; p < 0.001), whereas there were no differences in NSVD (57.8% vs. 54.0%; p = 0.52) or endocarditis (5.9% vs. 5.8%; p = 0.95). BVF rates were similar after SAVR and TAVR through 6 years (6.7% vs. 7.5%; p = 0.89). Conclusions: In the NOTION trial through 6 years, SVD was significantly greater for SAVR than TAVR, whereas BVF was low and similar for both groups. Longer-term follow-up of randomized clinical trials will be necessary to confirm these findings. (Nordic Aortic Valve Intervention Trial; NCT01057173)

OBJECTIVES Prosthesis-patient mismatch (PPM) after surgical aortic valve replacement (SAVR) for severe aortic valve stenosis (AVS) is common, but less common after transcatheter aortic valve replacement (TAVR) in patients considered at high risk for death after surgery. The objectives of this study were to determine incidence and clinical effect of PPM after SAVR and TAVR in a primarily low-risk patient group. METHODS Patients 70 years or older with severe isolated AVS, regardless of predicted operative mortality risk, were consecutively randomized 1:1 to TAVR using a self-expandable bioprosthesis (n = 145) or SAVR (n = 135). Post-procedure PPM was graded after 3 months as follows: Not present-mild, if indexed effective orifice area (iEOA) >0.85 cm2/m2, moderate, if 0.65 cm2/m2 < iEOA ≤ 0.85 cm2/m2 and severe, if iEOA ≤0.65 cm2/m2. Outcomes were major adverse cardiac and cerebrovascular events (MACCE, e.g. composite rate of all-cause death, stroke, myocardial infarction or valve reintervention), cardiac-related hospitalizations and New York Heart Association (NYHA) functional class after 2 years. RESULTS The incidence and the severity of PPM were significantly lower after TAVR compared with SAVR (severe, moderate, none-mild 14.0, 35.5, 50.4 vs 33.9, 36.7, 29.4%; P

Aim To assess the clinical outcome of patients with and without hereditary haemorrhagic telangiectasia (HHT) after embolisation of pulmonary arteriovenous malformations (PAVM) from a single national centre. Materials and methods The present register-based observational study including all patients with PAVM treated with embolisation at a reference centre for HHT and PAVM was undertaken over a 20-year period. Demographic data, HHT genotyping, clinical presentation, and outcome were registered. Patients with HHT were compared to the patients without HHT. Clinical examination, contrast-enhanced echocardiography, and computed tomography (CT) were used to assess the clinical outcome at follow-up. Results One hundred and thirty-six patients with 339 PAVM underwent embolisation during the study period: 22 did not have HHT; 62% had HHT1, 10% had HHT2, 4% had JP-HHT, 8% had clinical HHT without identified genetic mutations. Solitary PAVM were more common among patients without HHT than with HHT. Mean follow-up after the first embolisation was 58 months. Mean age at first embolisation was 46.5 years, and at last follow-up 51.8 years. The clinical success without shunt at follow-up was 87%. The 30-day mortality related to the embolisation was 0%. Twenty patients died during follow-up (mean age 69 years). Most patients could be treated during one session, but many will need a long follow-up with repeated clinical examinations and embolisation. Conclusion The majority of patients referred for embolisation of PAVM had HHT. Multiple PAVM is associated with HHT. Patients with PAVM should be screened for HHT and patients with HHT for PAVM. Embolisation is a safe procedure with high clinical success.

BackgroundThe Danish healthcare system has, as others, been subject of discussions of how it should be managed and rewarded (payment) to be most beneficial for society. Naturally this has been subject to the dominating political winds. Hospitals are run by the Regions. From 2002 to today the hospitals have been controlled using a base budget and activity-based costing, also known as the DRG-system). The DRG-system ensures that a ward receives a payment for each activity performed e.g. consultation, surgery etc. The DRG-system does not account for all payments and wards also receive a base pay. The DRG-system has been highly successful in increasing number of treated patients and consequently reducing waiting lists. However, the DRG-system is criticised for generating too much activity and incentivising treating of patients beyond need. The Capital Region has initiated 7 test projects with the purpose of developing, implementing and evaluating value-based care as alternative to the DRG-system. Material and Methods Project descriptions from 7 Danish test cases in the Capital Region was collected. The project descriptions were analysed. The analysis focused on incentives, cost-consequences and changes compared to current state. ConclusionsWe present key changes in costing and payment to the departments in the 7 projects. The projects share features and structure but appear to borrow KPI's and logic from the existing activity-based costing system. There appear to be a need for developing measures that can capture patient related outcomes and provide useful incentives for hospitals and staff. The current activity-based-costing favours generating activity while indirectly punishing more efficient treatment regimens with less activity. "You get what you measure" and there is a need to understand how value-based care affect behaviour.

PURPOSE:The potential benefits from respiratory gating (RG) compared to free-breathing (FB) regarding target coverage and dose to organs at risk for breast cancer patients receiving post-operative radiotherapy (RT) in the DBCG HYPO multicentre trial are reported.MATERIAL AND METHODS:Patients included in the DBCG HYPO trial were randomized between 50 Gy in 25 fractions (normofractionated) versus 40 Gy in 15 fractions (hypofractionated). A tangential forward field-in-field dose planning technique was used to cover the clinical target volume (CTV) with the intent to limit dose to the left anterior descending coronary artery (LADCA) to 20 Gy and 17 Gy in the normo- and hypofractionated arms, respectively. Treatment plan data for 1327 patients from four Danish centres was retrospectively analyzed. FB right-sided patients served as control group for the left-sided patients regarding CTV V95% (relative volume receiving at least 95% of the prescribed dose), mean heart dose (MHD) and mean lung dose (MLD).RESULTS:Median CTV V95% was for FB right-sided, FB left-sided and RG left-sided patients 94.6, 92.6 and 94.7% for normofractionated therapy, respectively, and 94.6, 91.8 and 94.4% for hypofractionated therapy and did not differ significantly for RG left-sided plans compared to FB right-sided in either study arm. CTV V95% was significantly lower for FB versus RG for left-sided plans in both arms. Median MHD was 0.7, 1.8 and 1.5 Gy (normofractionated therapy) versus 0.6, 1.5 and 1.2 Gy (hypofractionated therapy), respectively. The corresponding median MLD was 9.0, 8.3 and 7.3 Gy versus 7.3, 6.4 and 5.8 Gy, respectively.CONCLUSIONS:RG for left-sided breast cancer patients ensured similar CTV V95% as for FB right-sided patients. MLD was lower for RG due to the increased lung volume. MHD was generally low due to strict protocol-defined maximum dose to LADCA, but for left-sided patients RG led to significantly lower MHD. PURPOSE: The potential benefits from respiratory gating (RG) compared to free-breathing (FB) regarding target coverage and dose to organs at risk for breast cancer patients receiving post-operative radiotherapy (RT) in the DBCG HYPO multicentre trial are reported.MATERIAL AND METHODS: Patients included in the DBCG HYPO trial were randomized between 50 Gy in 25 fractions (normofractionated) versus 40 Gy in 15 fractions (hypofractionated). A tangential forward field-in-field dose planning technique was used to cover the clinical target volume (CTV) with the intent to limit dose to the left anterior descending coronary artery (LADCA) to 20 Gy and 17 Gy in the normo- and hypofractionated arms, respectively. Treatment plan data for 1327 patients from four Danish centres was retrospectively analyzed. FB right-sided patients served as control group for the left-sided patients regarding CTV V95% (relative volume receiving at least 95% of the prescribed dose), mean heart dose (MHD) and mean lung dose (MLD).RESULTS: Median CTV V95% was for FB right-sided, FB left-sided and RG left-sided patients 94.6, 92.6 and 94.7% for normofractionated therapy, respectively, and 94.6, 91.8 and 94.4% for hypofractionated therapy and did not differ significantly for RG left-sided plans compared to FB right-sided in either study arm. CTV V95% was significantly lower for FB versus RG for left-sided plans in both arms. Median MHD was 0.7, 1.8 and 1.5 Gy (normofractionated therapy) versus 0.6, 1.5 and 1.2 Gy (hypofractionated therapy), respectively. The corresponding median MLD was 9.0, 8.3 and 7.3 Gy versus 7.3, 6.4 and 5.8 Gy, respectively.CONCLUSIONS: RG for left-sided breast cancer patients ensured similar CTV V95% as for FB right-sided patients. MLD was lower for RG due to the increased lung volume. MHD was generally low due to strict protocol-defined maximum dose to LADCA, but for left-sided patients RG led to significantly lower MHD.

BACKGROUND Transcatheter aortic valve replacement (TAVR) is an option in certain high-risk surgical patients with severe aortic valve stenosis. It is unknown whether TAVR can be safely introduced to lower-risk patients.

BACKGROUND: As patients with severe aortic valve stenosis (AS) develop symptoms their survival decreases rapidly, if treated conservatively. Transcatheter aortic valve implantation (TAVI) has been introduced as a less invasive treatment alternative, especially in inoperable patients, who often have severe comorbidities, including chronic obstructive pulmonary disease (COPD).MATERIALS AND METHODS: Since the beginning of our TAVI program in March 2008, data on all 131 TAVI patients were prospectively and consecutively collected in this registry with complete follow-up. COPD was present in 37 patients. By January 2012 survival data were collected from the Danish Civil Registration System. Median follow-up duration was 559 days.RESULTS: Overall survival and survival from cardiac death was equivalent in both patients with and without COPD (p = 0.98 and p = 0.26) in the follow-up period. Further, patients with COPD had higher New York Heart Association (NYHA) class prior to intervention compared with those without (3.1 ± 0.5 vs. 2.9 ± 0.5, p = 0.02). In multivariate regression analysis COPD was associated with 30-day postoperative NYHA class (0.43; 95% confidence interval (CI): 0.10-0.75; p = 0.01), but not to NYHA class improvement from pre- to postintervention (0.25; 95% CI: - 0.12 to -0.63; p = 0.18).CONCLUSIONS: In patients with symptomatic severe AS treated with TAVI, the presence of COPD neither affects overall survival nor survival from cardiac death. Patients with COPD had, however, both higher pre- and postoperative NYHA class compared with patients without COPD, but NYHA class improvement from pre- to postintervention was equivalent in both groups.

No published studies have compared the outcome after transcatheter aortic valve implantation (TAVI) with the outcome in the general population. Thus, it is unknown whether TAVI restores normal life expectancy and stroke risk. Furthermore, despite the increasing use of TAVI, only little is known about the temporal trends for TAVI regarding patient characteristics and outcomes. We identified all Danish patients treated with TAVI from 2006 to 2014 (n = 1,631) and 9,737 general population controls matched by gender, age, and co-morbidity. The primary end point was a composite end point of all-cause mortality and stroke. During the first 90 days, the risk of the combined end point, the stroke risk, and mortality were significantly higher among TAVI patients compared with controls (9.4%, 7.5%, and 2.5%, respectively, in TAVI patients compared with 2.0%, 1.6%, and 0.5% in controls). After 90 days, there were no differences (adjusted mortality rate ratio, stroke rate ratio, and mortality or stroke rate ratio 0.92 [0.79 to 1.06], 1.32 [0.98 to 1.78], and 1.00 [0.90 to 1.10], respectively). During the study period, there were small changes in the characteristics of patients treated with TAVI; however, more patients were treated by transfemoral access; fewer needed blood transfusions, hospital stays were shorter, and the overall mortality rate decreased. In conclusion, 90 days after TAVI, the stroke risk and mortality of the TAVI patients were comparable with the stroke risk and mortality of the general population. Over time, the patient risk profiles have remained largely unchanged; however, outcomes have improved substantially, including lower short- and long-term mortality.

Interventional cardiology in Denmark has been carried out since the mid 1980s. Interventional cardiology is only performed at a few high-volume centres. Healthcare coverage is universal and is essentially free of charge. Hospitals are mostly publicly owned and financed by fixed budgets and, in part, an activity-based funding system. Approximately 30,000 coronary angiographies (CAG), 10,000 percutaneous coronary interventions (PCIs) of which approximately 25% are primary PCIs, and 500 transcatheter aortic valve implantations (TAVIs) are carried out each year. The numbers of CAG and PCI have reached a plateau in recent years, whereas structural heart interventions, in particular TAVI, are increasing. Around 90% of all patients treated with PCI have a stent implanted, with more than 95% of these being drug-eluting stents. There is a low but increasing use of bioabsorbable scaffolds and drug-eluting balloons.

Pathogenic germline mutations in ELN can be detected in patients with supravalvular aortic stenosis. The mutation might occur de novo or be inherited following an autosomal dominant pattern of inheritance. In this report we describe a three-generation family suffering from supravalvular aortic stenosis, various other arterial stenoses, sudden death, and intracranial aneurysms. A frameshift mutation in exon 12, not described before, was detected in the affected family members. This report emphasises the importance of family history, genetic counselling, and demonstrates the great variability in the phenotype within a single SVAS family.

Background Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease characterized by a wide variety of clinical manifestations, including pulmonary arteriovenous malformations (PAVMs), which due to paradoxical embolization may cause cerebral abscess. Objective To estimate the risk of cerebral abscess among patients with HHT. Methods All patients with HHT included in the Danish HHT data base, between January 1995 and October 2012, have been clinically evaluated for the presence of neurological symptoms and history of previous cerebral abscess. Results A total of 337 patients with HHT have been included in the Danish database. Of these, 264 were screened for the presence of PAVM. In 117 patients, a PAVM was diagnosed; among these, we identified nine patients with a history of cerebral abscess. The prevalence of cerebral abscess among patients with HHT and PAVM was therefore 7.8%. The patients with a history of cerebral abscess were genetically evaluated, and seven had ENG mutations, one had an ALK1 mutation, and in one case, a mutation could not be identified. Conclusion Patients with untreated PAVM have a considerable risk of sustaining cerebral abscesses. A cerebral abscess may be the first symptom leading to an HHT diagnosis. Patients with unexplained cerebral abscess should be evaluated for HHT and PAVM.

Background— Transcatheter valve implantation inside failed bioprosthetic surgical valves (valve-in-valve [ViV]) may offer an advantage over reoperation. Supra-annular transcatheter valve position may be advantageous in achieving better hemodynamics after ViV. Our objective was to define targets for implantation that would improve hemodynamics after ViV. Methods and Results— Cases from the Valve-in-Valve International Data (VIVID) registry were analyzed using centralized core laboratory assessment blinded to clinical events. Multivariate analysis was performed to identify independent predictors of elevated postprocedural gradients (mean ≥20 mm Hg). Optimal implantation depths were defined by receiver operating characteristic curve. A total of 292 consecutive patients (age, 78.9±8.7 years; 60.3% male; 157 CoreValve Evolut and 135 Sapien XT) were evaluated. High implantation was associated with significantly lower rates of elevated gradients in comparison with low implantation (CoreValve Evolut, 15% versus 34.2%; P =0.03 and Sapien XT, 18.5% versus 43.5%; P =0.03, respectively). Optimal implantation depths were defined: CoreValve Evolut, 0 to 5 mm; Sapien XT, 0 to 2 mm (0–10% frame height); sensitivities, 91.3% and 88.5%, respectively. The strongest independent correlate for elevated gradients after ViV was device position (high: odds ratio, 0.22; confidence interval, 0.1–0.52; P =0.001), in addition to type of device used (CoreValve Evolut: odds ratio, 0.5; confidence interval, 0.28–0.88; P =0.02) and surgical valve mechanism of failure (stenosis/mixed baseline failure: odds ratio, 3.12; confidence interval, 1.51–6.45; P =0.002). Conclusions— High implantation inside failed bioprosthetic valves is a strong independent correlate of lower postprocedural gradients in both self- and balloon-expandable transcatheter valves. These clinical evaluations support specific implantation targets to optimize hemodynamics after ViV.

Background— The Nordic Aortic Valve Intervention (NOTION) trial was the first to randomize all-comers with severe native aortic valve stenosis to either transcatheter aortic valve replacement (TAVR) with the CoreValve self-expanding bioprosthesis or surgical aortic valve replacement (SAVR), including a lower-risk patient population than previous trials. This article reports 2-year clinical and echocardiographic outcomes from the NOTION trial. Methods and Results— Two-hundred eighty patients from 3 centers in Denmark and Sweden were randomized to either TAVR (n=145) or SAVR (n=135) with follow-up planned for 5 years. There was no difference in all-cause mortality at 2 years between TAVR and SAVR (8.0% versus 9.8%, respectively; P =0.54) or cardiovascular mortality (6.5% versus 9.1%; P =0.40). The composite outcome of all-cause mortality, stroke, or myocardial infarction was also similar (15.8% versus 18.8%, P =0.43). Forward-flow hemodynamics were improved following both procedures, with effective orifice area significantly more improved after TAVR than SAVR (effective orifice area, 1.7 versus 1.4 cm 2 at 3 months). Mean valve gradients were similar after TAVR and SAVR. When patients were categorized according to Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) (P =0.58) or intermediate-risk patients (21.1% versus 27.1%; P =0.59). Conclusions— Two-year results from the NOTION trial demonstrate the continuing safety and effectiveness of TAVR in lower-risk patients. Longer-term data are needed to verify the durability of this procedure in this patient population. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01057173.

Estimates of the prevalence of congenital heart defects (CHD) have been published over many years and from many regions. As they are based on different definitions of which cases to include in the CHD prevalence, published prevalence estimates vary substantially. With the increasing use of echocardiography in neonatal intensive care, a patent ductus arteriosus (PDA) or flow over the atrial septum will often be visible. These findings may be coded as CHD at discharge and in this way falsely increase the CHD prevalence in the population. There are several purposes for which population-based data on CHD may be used: etiology, planning of treatment, or obtain information on outcome, including mortality. For etiology studies, it is important to include terminations of pregnancy as well as all births with CHD. For mortality studies in live births, inclusion of preterm born infants with PDA will increase overall mortality of CHD. The Danish Register of Congenital Heart Disease is based on hospital discharge diagnoses and diagnoses from outpatient visits. To increase the validity of these data, extensive data cleaning has been carried out based on record review and knowledge on the discharge coding practice. We include PDA and atrial septal defects as CHD cases if these defects are still open 2 months after birth. International consensus on how to define CHD would improve the validity and comparability of epidemiological studies on CHD.

Purpose Changes in Apparent Diffusion Coefficient (ADC) intensities derived from Magnetic Resonance (MR) imaging have been shown to be potentially predictive of (chemo) radiotherapy response in rectal cancer. Radiomics is a non-invasive, computer-assisted extraction of image-based biomarkers that assist in characterization of tumour phenotype. This study concerns the identification and selection of robust (i.e. repeatable and reproducible) radiomic features in MR-ADC across independent scanners in The Netherlands and Denmark. Methods Retrospective datasets (23 cases from the THUNDER clinical trial and 34 cases from a Danish watchful-waiting protocol) were independently manually delineated. Radiomic features were extracted using public open source software. Repeatability was examined by test-retest using scans 5 min apart. Reproducibility was assessed using concordance and intra-class correlation coefficients for sensitivity to inter-observer disagreement, image re-processing and effect of image filters. Results Significant intra-class correlations were observed between related sets of features. Histogram-based features were least sensitive to variations with respect to resampling and quantization (78% and 89% of features, respectively, exceeding the highest reproducibility criterion). Global robustness was adversely affected by image filtering and differences in manual delineation. Shape metrics were highly sensitive to inter-observer variability, but were insensitive to differences in image pre-processing. Textural features exhibited the highest sensitivity to processing steps, for all of the examined options. A number of radiomic features were found to be correlated with tumour volume, which should be a noted as a potential confounder for future radiomics studies. Conclusions This study showed that radiomic features were differentially affected by specific choices made along the processing pathway. In general, histogram features were least sensitive to details of processing, while shape metrics and textural features are more susceptible to heterogeneity in delineation, slice thickness and filtration. The latter was most likely due to its reliance on subtly nuanced properties within the image. Identification and selection of robust radiomic metrics are essential for development of clinically actionable prognostic models for rectal cancer incorporating image-based biomarkers.

We have recently developed a simple mutation screening assay based on the denaturing gradient gel electrophoresis (DGGE) technique for detection of mutations in the coding and regulatory regions of the low density lipoprotein receptor (LDLR) gene and the codon 3500 region of the apolipoprotein (apo) B-100 gene leading to familial hypercholesterolemia (FH) and familial defective apo B-100 (FDB), respectively. To evaluate the assay, 14 Danish families suspected of FH were studied. In ten families, the DGGE assay detected seven different point mutations, including mutations undescribed prior to establishing the assay. In addition, in one of these ten families and in one of the remaining four families, Southern blotting detected the FH-DK3 exon 5 deletion. Based on segregation analysis and clinical data, the FH diagnosis was dubious in the remaining three families without DGGE or Southern blotting detectable mutations. In conclusion, a simple DGGE based mutation screening assay may detect underlying mutations in most FH/FDB families, thus allowing its routine use in genetic counselling of FH-families.

CERN (European Organization for Nuclear Research) is an international particle physics laboratory located in Geneva, Switzerland. CERN carries out fundamental research in particle and nuclear physics using several large particle accelerators, including the Large Hadron Collider (CERN 2015).

We describe a case of transcatheter aortic valve implantation (TAVI) using the LUCAS® Chest Compression System in an elderly high risk patient with severe aortic stenosis and heart failure. In this case, the patient developed severe aortic regurgitation following predilatation of the native aortic valve and automated cardiopulmonary resuscitation (A-CPR) was initiated. The procedure was performed under ongoing A-CPR for a total of 28 min. The patient was transferred to the intensive care unit and to a step down unit the following day. At follow-up 30 days later, she showed no signs of neurologic or cardiac damage. This case report shows, that it is possible to perform the TAVI procedure under ongoing A-CPR and that A-CPR, judged by invasive blood pressures, was capable of maintaining a satisfactory perfusion pressure even with a damaged aortic valve.

Platypnoea-orthodeoxia is a relatively unknown syndrome characterized by dyspnoea and arterial desaturation during the transition from a lying to an uprighth position by right to left shunting of blood without increased blood pressure in the right atrium. The condition is assumed to be underdiagnosed because of challenging diagnostics. This case describes a woman who, despite extensive investigation, remained undiagnosed for years. The diagnosis should be kept in mind when treating unexplained desaturation.

ObjectiveWe aimed to assess cancer risk in congenital heart defect patients, with and without Down's syndrome, compared with the general population.MethodsWe identified all patients born and diagnosed with congenital heart defects from 1977 to 2008 using the Danish National Registry of Patients, covering all Danish hospitals. We compared cancer incidence in the congenital heart defect cohort with that expected in the general population (∼5.5 million) using the Danish Cancer Registry, and computed age- and gender-standardised incidence ratios.ResultsWe identified 15,905 congenital heart defect patients, contributing a total of 151,172 person-years at risk; the maximum length of follow-up was 31 years (median 8 years). In all, 53 patients were diagnosed with cancer, including 30 female and 23 male patients (standardised incidence ratio = 1.63; 95% confidence interval: 1.22–2.13). Risks were increased for leukaemia, brain tumours, and basal cell carcinoma. After excluding 801 patients with Down's syndrome, the standardised incidence ratio was 1.19 (95% confidence interval: 0.84–1.64). In the subgroup of 5660 non-Down's syndrome patients undergoing cardiac surgery or catheter-based interventions, the standardised incidence ratio was 1.45 (95% confidence interval: 0.86–2.29).ConclusionThe overall risk of cancer among congenital heart defect patients without Down's syndrome was not statistically significantly elevated. Cancer risk in the congenital heart defect cohort as a whole, including patients with Down's syndrome, was increased compared with the general population, although the absolute risk was low. Studies with longer follow-up and more information on radiation doses are needed to further examine a potential cancer risk associated with diagnostic radiation exposure.

Familial hypercholesterolaemia (FH) is an autosomal co-dominantly inherited condition resulting from mutations of the low-density lipoprotein (LDL) receptor which occur in heterozygous form in approximately one in 500 individuals. Clinically, FH is characterized by 2-3-fold elevation of serum LDL cholesterol levels, accelerated development of atherosclerotic vascular disease, and, if untreated, shortened lifespan. The Finnish population, which represents a genetic isolate, offers exceptional possibilities for genetic-epidemiological studies on FH, as a handful of founder gene mutations account for the majority of FH cases in Finland. This review summarizes data from our FH studies carried out since 1985. We wish to emphasize the continuum of genotype-phenotype relationships, the importance of molecular diagnosis, the detection of novel risk factors of vascular disease, and innovations inhibiting cholesterol absorption for the modern treatment of FH.