BACKGROUND:Accurate risk stratification for patients with three-vessel coronary artery disease (3VD) undergoing percutaneous coronary intervention (PCI) remains important in contemporary practice. SYNTAX-based mortality prediction models require reassessment in modern PCI populations. METHODS:This post-hoc analysis of the Multivessel TALENT trial evaluated the core and extended logistic clinical SYNTAX Score (LCSS) for predicting 1-year all-cause mortality. Discrimination was assessed using the area under the receiver-operating characteristic curve (AUC), and calibration using calibration intercept, calibration slope, graphical calibration, and the E-statistic. Prediction scores were calculated within each of 20 imputed datasets, with model performance evaluated within each imputation and summarised across imputations. Intercept-and-slope recalibration and decision curve analysis were also performed. RESULTS:At 1 year, 46 (3.0%) of 1,548 enrolled patients had died. The pooled AUCs were 0.716 for the LCSS core model and 0.744 for the extended model, compared with 0.629 for the anatomical SYNTAX Score and 0.632 for the functional SYNTAX Score. LCSS models systematically overestimated absolute risk, although observed mortality increased across predicted-risk quintiles. Decision curve analysis showed a positive net benefit for the original and recalibrated LCSS models across threshold probabilities of 1% to 10%, with numerically higher net benefit for the recalibrated extended model across much of the evaluated threshold range. CONCLUSION:In contemporary PCI for 3VD, the LCSS showed moderate discrimination for 1-year all-cause mortality while overestimating its absolute risk. Recalibration improved agreement with observed risk in this cohort and may inform future validation and model refinement.

Minimally invasive transcatheter aortic valve replacement (TAVR) has become the preferred procedure for patients with aortic valve stenosis or insufficiency who are at high risk for conventional open-heart surgery. The favorable clinical outcomes observed in high-risk patients have led to an expansion of the eligible cohort, now including intermediateand low-risk patients. A critical aspect of advancing TAVR procedures lies in preoperative simulation, which in future can integrate patient-specific in-silico deployment simulations and post-deployment fluid mechanics assessments. In light of the aforementioned context, this study investigates the volumetric distribution of calcifications in the aortic cusps of a TAVR patient population and explores whether naturally occurring clusters should be considered in in-silico simulations. We analyze clustering results based on different methods for feature extraction, using circular measured volumetric calcification distributions. The clustering method applied is hierarchical clustering. Our findings identify distinct calcification clusters across different feature extraction methods. The Framework can be incorporated into in-silico trials and clinical studies assessing the impact of calcification patterns on clinical outcomes and TAVR device optimization.

Transcatheter Aortic Valve Replacement (TAVR) is a widely used treatment for severe aortic stenosis, particularly in patients with a high surgical risk. Although initially designed for tricuspid aortic valves (TAV), its use in bicuspid aortic valves (BAV) presents unique challenges due to anatomical variations and extensive calcifications, which can hinder optimal stent expansion. In this study, a prototype of an elliptical TAVR stent was produced. Radial force measurements were carried out to calibrate the simulation model. In addition, the deployment behaviour of this elliptical TAVR stent was investigated in a patientspecific bicuspid aortic valve geometry with severe calcification. Finite Element (FE) simulations were conducted to analyze the crimping and expansion process of an elliptical TAVR stent. Expansion behavior and radial force behavior were compared with a conventional circular stent design. The simulation results demonstrate that both stents exhibit elliptical deformation due to calcification-induced constraints. However, the elliptical stent experiences less deformation in the narrowest regions, potentially reducing leaflet stress and improving valve function. The elliptical design may enhance the longterm durability of the artificial valve. The findings highlight the potential benefits of elliptical TAVR stents for bicuspid anatomies. Further investigations, including large-scale in silico studies are necessary to optimize stent design and improve clinical outcomes for bicuspid valve patients.

BACKGROUND:Multivessel coronary artery disease (CAD) is present in 30% to 70% of patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) depending on varying age and risk profiles. In contrast to the STEMI cohort, there is only limited scientific evidence derived from randomized controlled trials directing the general decision for or against complete revascularization in the NSTEMI population. PRIMARY HYPOTHESIS:The COMPLETE-NSTEMI trial aims to investigate whether multivessel percutaneous coronary intervention (PCI) is superior over culprit-lesion only PCI in patients with NSTEMI and multivessel CAD. DESIGN:COMPLETE-NSTEMI is a prospective, randomized, controlled, multicenter, parallel group, open-label trial. It will enroll 3390 NSTEMI patients with multivessel CAD at 65 to 70 sites in Germany and Austria. Patients will be randomized 1:1 to either complete revascularization with PCI or culprit lesion-only PCI. ENDPOINTS:The primary efficacy endpoint is a composite of cardiovascular death or rehospitalization for nonfatal myocardial infarction during follow-up. The trial is event-driven and will be stopped as soon as 578 primary endpoint events and a minimal follow-up duration of 12 months for each patient are reached. CURRENT STATUS:The first patient was enrolled at October 27, 2023. By April 2025, 51 sites have been activated and >500 patients have been randomized. Completion of recruitment is expected for the first half of 2027. The final results of the primary endpoint are expected in 2028. OUTLOOK:COMPLETE NSTEMI will be the first dedicated trial to answer the question about the optimal revascularization strategy in patients with NSTEMI and multivessel CAD. TRIAL REGISTRATION:CLINICALTRIALS.GOV: NCT05786131.

Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of severe aortic stenosis, yet paravalvular leakage (PVL) remains a significant complication, associated with increased mortality. Clinical studies have identified correlations between PVL and both anatomical features and calcification patterns. Numerical simulations, particularly patient-specific models, offer valuable insights into PVL, but the limited scale of these studies hinders robust statistical analysis. This study introduces a novel in silico clinical trial (ISCT) framework to investigate the correlation between calcification severity, localization and PVL. For this purpose, a synthetic cohort of calcified aortic roots was generated. A conditional convolutional variational autoencoder was used to create calcification patterns for an existing virtual cohort of the aortic root. The workflow includes finite element analyses for pre-dilation and deployment simulations as well as computational fluid dynamic simulations for PVL calculations of 243 virtual TAVR patients. The results show that the absolute amount of calcification in the device landing zone has no significant influence, but its regional distribution does, especially in the combined leaflet regions. In addition, sinotubular junction diameter, annular eccentricity index, oversizing as well as the combination of aortic angle and calcification in the combined non and left coronary leaflet region influence the occurrence of PVL. This framework not only advances our understanding of PVL mechanisms but also demonstrates the potential of ISCT to complement traditional clinical studies, enabling systematic exploration of complex factors influencing TAVR outcomes.

Angiogenesis is crucial in myocardial healing after myocardial infarction (MI). The αvβ3-integrin, a key regulator of angiogenesis, is targeted by RGD-based PET tracers like [68Ga]Ga-NODAGA-RGD. Yet, angiogenesis imaging using RGD-based tracers is seriously hampered by the lack of true specificity of the αvβ3-integrin for angiogenic cells. Therefore, our study aimed to identify the cell type with the highest αvβ3-integrin expression in the process of myocardial healing in order to determine the actual value of the PET tracer [68Ga]Ga-NODAGA-RGD for imaging post-MI angiogenesis. Cardiac magnetic resonance imaging (CMR) was used to assess cardiac function and morphology after 28 days in two groups: permanent ligation (PL) of the left anterior descending coronary artery and transient occlusion for 30 min (I/R). Following these measurements, hearts were excised for histological and immunohistological examinations to evaluate scar formation, capillary density, and cellular composition. PET imaging with [68Ga]Ga-NODAGA-RGD was conducted on day 5 and day 7 post-MI. Single-nucleus transcriptomics were performed to identify cell clusters expressing αvβ3-integrin. Both infarct models induced scar formation, with the PL group developing large infarcts accompanied by massive left ventricular dilation and hypertrophy of cardiomyocytes, while the I/R group exhibited small intramural scars without significant changes in LV geometry or function. PET imaging revealed significantly higher tracer accumulation in the infarct area of the PL group compared to the I/R group. Single-nucleus transcriptomics performed 5 days post-MI revealed that angiogenesis markers were enriched in the I/R group, while the highest αvβ3-integrin mRNA expression was identified in the fibroblast cluster, indicating an activated phenotype. Activated fibroblasts are the primary target cells of [68Ga]Ga-NODAGA-RGD, rather than angiogenic cells. In this regard, [68Ga]Ga-NODAGA-RGD is most probably not a valid tracer for imaging angiogenesis during the first days post-MI.

Background: The RESHAPE-HF2 trial is aimed at evaluating the efficacy of the MitraClip device for the treatment of clinically significant functional mitral regurgitation (FMR) in patients with heart failure (HF). This report describes the baseline echocardiographic characteristics of patients enrolled in the RESHAPE-HF2 trial compared to those enrolled in the COAPT and MITRA-FR trials. Methods: The RESHAPE-HF2 study is a prospective, randomized, multicenter trial involving patients with symptomatic HF, a left ventricular ejection fraction (LVEF) between 20% and 50%, and moderate-to-severe or severe FMR who are ineligible for isolated mitral valve surgery, despite receiving guideline-directed therapy. Patients were randomized 1:1 to either receive the MitraClip or be placed in a control group without the intervention. Results: For the 505 patients randomized (mean age 70 years, 20% female, mean body mass index 26.8 kg/m2), the mean LVEF in the cohort was 31±8%. The mean regurgitant volume was 37±12 mL, while mean proximal iso-velocity surface area (PISA) radius was 0.72 cm. Less than half of the patients (44%) had MR severity grade 4+. The mean effective regurgitant orifice area (EROA) among patients in RESHAPE-HF2 (0.25 cm2) was lower compared to patients in MITRA-FR (0.31 cm2) and in COAPT (0.40 cm2) trials. Regurgitant volumes in RESHAPE-HF2 were 18% lower than in than in MITRA-FR (45 mL) but 38% higher than in COAPT (27 mL). The mean LV end-diastolic volumes values in the RESHAPE-HF2, COAPT, and MITRA-FR trials were 211 mL, 193 mL, and 250 mL, respectively. Patients in RESHAPE-HF2 (41 mmHg) had a comparatively lower right ventricular systolic pressure than patients in MITRA-FR (54 mmHg) and in COAPT (44 mmHg). Patients in RESHAPE-HF2, MITRA-FR, and COAPT had a similar LVEF of around 31%. Conclusions: The baseline echocardiographic characteristics of patients in the RESHAPE-HF2 trial differ from patients in the MITRA-FR and COAPT trials. Patients enrolled in RESHAPE-HF2 had moderate-to-severe FMR, characterized by a smaller PISA radius, a lesser proportion of MR severity grade of 4+, and lower mean EROA and regurgitant volumes compared to patients in COAPT and MITRA-FR trials. LVEF was largely similar across all trials. RESHAPE-HF2 is testing TEER in a third distinct cohort of patients who have less severe FMR compared to patients in COAPT trial but have high left atrial volumes. The RESHAPE-HF2 population is also echocardiographically different from the MITRA-FR cohort.

Due to promising results, the patient cohort for transcather aortic valve replacement (TAVR) has been extended in recent years to include patients with a bicuspid aortic valve (BAV). There are different types of BAV. One variant is the tricommisural bicuspid aortic valve (TBAV). BAV have an increased risk of post-TAVR complications such as paravalvular leakage. In the case of paravalvular leakage, blood flows past the prosthesis back into the ventricle during diastole. Clinically, patients with BAV are often pre-dilated. For this reason, we want to investigate how pre-dilatation of BAV can affect the leakage rate. A simplified model is used for pre-dilatation, where the calcification nodule is cut along the free edge of the leaflets before the deployment. In order to evaluate the effects of this method, a deployment simulation was carried out for both geometries using an explicit calculation. A flow simulation was then performed to determine the paravalvular leakage. The pre-dilatation allows the leaflets to move independently of each other. Without pre-dilatation, the TAVR cannot fully expanded. The leakage rate is higher for the BAV than for the pre-dilated geometry (53.1mLs−1 vs. 19.4mLs−1). In this model, we have shown the effect of pre-dilatation on implantation results.

Transcatheter aortic valve replacement (TAVR) has become the standard treatment of multimorbid patients with severe aortic valve stenosis. One frequently observed complication after TAVR procedure is the occurence of paravalvular leakage (PVL). PVL is caused by a gap between the vessel wall and the TAVR stent, enabling blood to flow from the aorta back to the ventricle during diastolic phase. A high PVL rate leads to increased mortality of TAVR patients. To avoid this complication, pericardial skirts were developed by manufacturers to seal the leakage gap. Furthermore, the aim is to improve the conforming expansion of the TAVR stent to the vessel wall, especially for the self-expanding TAVR consisting of nitinol. One factor for the expansion is the size and shape of the TAVR stent cells, which vary between 9 and 15 cells in the circumferential direction for established TAVR devices. To quantify the impact of different cell sizes on the occurence of PVL, we performed numerical studies with different TAVR designs and investigated the PVL for each TAVR design. For this purpose, we developed three different TAVR designs with 9, 12 and 15 stent cells in the circumferential direction of the TAVR. These were deployed into a generic aortic root model with standardized calcification in the annulus region using finite element simulations. Afterwards, the PVL was calculated using numerical flow simulations. We found that the TAVR stent design with nine cells had the highest PVL rate (11.2mLs−1). In contrast, the TAVR stent design with 15 cells had the lowest PVL (4.8mLs−1). Our study thus showed a decisive impact of cell size on the sealing behavior of the TAVR stent and, accordingly, the PVL.

BACKGROUND:For patients with functional mitral regurgitation (FMR) and symptomatic heart failure (HF), randomized trials of mitral transcatheter edge-to-edge repair (M-TEER) have produced conflicting results. OBJECTIVES:This study sought to assess the impact of M-TEER on hospitalization rates, and explore the effects of M-TEER on patients who did or did not have a history of recent HF hospitalizations before undergoing M-TEER. METHODS:RESHAPE-HF2 (Randomized Investigation of the MitraClip Device in Heart Failure: 2nd Trial in Patients with Clinically Significant Functional Mitral Regurgitation) included patients with symptomatic HF and moderate to severe FMR (mean effective regurgitant orifice area 0.25 cm2; 14% >0.40 cm2, 23% <0.20 cm2) and showed that M-TEER reduced recurrent HF hospitalizations with and without the addition of cardiovascular (CV) death and improved quality of life. We now report the results of prespecified analyses on hospitalization rates and for the subgroup of patients (n = 333) with a HF hospitalization in the 12 months before randomization. RESULTS:At 24 months, the time to first event of CV death or HF hospitalization (HR: 0.65; 95% CI: 0.49-0.85; P = 0.002), the rate of recurrent CV hospitalizations (rate ratio [RR]: 0.75; 95% CI: 0.57-0.99; P = 0.046), the composite rate of recurrent CV hospitalizations and all-cause mortality (RR: 0.74; 95% CI: 0.57-0.95; P = 0.017), and of recurrent CV death and CV hospitalizations (RR: 0.76; 95% CI: 0.58-0.99; P = 0.040), were all lower in the M-TEER group. The RR of recurrent hospitalizations for any cause was 0.82 (95% CI: 0.63-1.07; P = 0.15) for patients in the M-TEER group vs control group patients. Patients randomized to M-TEER lost fewer days due to death or HF hospitalization (13.9% [95% CI: 13.0%-14.8%] vs 17.4% [95% CI: 16.4%-18.4%] of follow-up time; P < 0.0001, and 1,067 vs 1,776 total days lost; P < 0.0001). Patients randomized to M-TEER also had better NYHA functional class at 30 days and at 6, 12, and 24 months of follow-up (P < 0.0001). A history of HF hospitalizations before randomization was associated with worse outcomes and greater benefit with M-TEER on the rate of the composite of recurrent HF hospitalizations and CV death (Pinteraction = 0.03) and of recurrent HF hospitalizations within 24 months (Pinteraction = 0.06). CONCLUSIONS:These results indicate that a broader application of M-TEER in addition to optimal guideline-directed medical therapy should be considered among patients with symptomatic HF and moderate to severe FMR, particularly in those with a history of a recent hospitalization for HF.

Minimally invasive transcatheter aortic valve replacement (TAVR) procedure has become the preferred procedure for patients with aortic valve stenosis or insufficiency with high risk for conventional open surgery. The favorable clinical outcomes of high-risk patients led to an expansion of the cohort including intermediate and low-risk patients. A critical aspect of advancing TAVR procedures lies in preoperative planning, integrating patient-specific in-silico deployment simulation and post-deployment fluid mechanics assessments. This study introduces a novel approach to calcified TAVR patient shape modeling, addressing this problems. The model integrates an extended mesh generated by DeepCarve, encompassing the aortic arch, and a novel deep learning-based volumetric shape model of calcifications. The key innovation lies in the utilization of a conditional Convolutional Variational Autoencoder (cCVAE) to generate realistic calcification patterns, demonstrating promising preliminary results in matching actual cohort data. Future investigations should focus on data collection from diverse medical centers to validate and refine the proposed methodology. This study showcases significant progress in generating synthetic TAVR patient geometries, incorporating detailed anatomical structures such as the aortic root, valve, and arch, along with volumetric calcification patterns. These findings represent a crucial step towards enabling real-time preoperative TAVR planning, inclusive of patient- specific in-silico deployment simulation and comprehensive fluid mechanics assessments.

Transcatheter aortic valve implantation (TAVI) for aortic valve stenosis can be seen as a disruptive technology that has become the standard treatment for previously inoperable patients over the past 15 years. A key component of the development process for new transcatheter aortic valve replacements (TAVR) is the hydrodynamic testing as part of real-time functional testing. Although, fundamental requirements, necessary testing methods, as well as functional environments, physiological and pathophysiological stress situations, are defined, resulting testing parameter ranges are only estimated. For this reason, two clinically established TAVR were tested in different parameter settings representing different characteristic load situations on a patient. In fact, the two TAVR with different dilatation concepts were tested under different cardiac outputs (CO) and the resulting effective orifice area (EOA), the closing and the leakage volume was measured and evaluated according to ISO 5840-3:2021. Regarding the two TAVR designs, it can be shown that the high radial force of the Lotus Valve contributes to an improvement in the sealing effectiveness of the TAVR. This is because the annulus can be pushed outward by the stent resulting in a better fit between the TAVR and the vessel wall. Additionally, the lamellar skirt of the Lotus Valve also appears to contribute to improved sealing. In the presented experiments, the smooth abluminal- mounted pericardial skirt of the Evolut PRO bioprosthesis does not seem to contribute to additional sealing. The developed test procedure aims to contribute to the establishment of new in vitro standards. Future work must involve applying the testing methods to additional clinically established TAVR as well as new developments.

Background The initial idea of functional tissue replacement has shifted to the concept that injected cells positively modulate myocardial healing by a non-specific immune response of the transplanted cells within the target tissue. This alleged local modification of the scar requires assessment of regional properties of the left ventricular wall in addition to commonly applied measures of global morphological and functional parameters. Hence, we aimed at investigating the effect of cardiac cell therapy with cardiovascular progenitor cells, so-called cardiac induced cells, on both global and regional properties of the left ventricle by a multimodal imaging approach in a mouse model. Methods Myocardial infarction was induced in mice by ligation of the left anterior descending artery, the therapy group received an intramyocardial injection of 1 × 10 6 cardiac induced cells suspended in matrigel, the control group received matrigel only. [ 18 F]FDG positron emission tomography imaging was performed after 17 days, to assess regional glucose metabolism. Three weeks after myocardial infarction, cardiac magnetic resonance imaging was performed for morphological and functional assessment of the left ventricle. Following these measurements, hearts were excised for histological examinations. Results Cell therapy had no significant effect on global morphological parameters. Similarly, there was no difference in scar size and capillary density between therapy and control group. However, there was a significant improvement in contractile function of the left ventricle – left ventricular ejection fraction, stroke volume and cardiac output. Regional analysis of the left ventricle identified changes of wall properties in the scar area as the putative mechanism. Cell therapy reduced the thinning of the scar and significantly improved its radial contractility. Furthermore, the metabolic defect, assessed by [ 18 F]FDG, was significantly reduced by the cell therapy. Conclusion Our data support the relevance of extending the assessment of global left ventricular parameters by a structured regional wall analysis for the evaluation of therapies targeting at modulation of healing myocardium. This approach will enable a deeper understanding of mechanisms underlying the effect of experimental regenerative therapies, thus paving the way for a successful translation into clinical application.

AIM:The RESHAPE-HF2 trial is designed to assess the efficacy and safety of the MitraClip device system for the treatment of clinically important functional mitral regurgitation (FMR) in patients with heart failure (HF). This report describes the baseline characteristics of patients enrolled in the RESHAPE-HF2 trial compared to those enrolled in the COAPT and MITRA-FR trials. METHODS AND RESULTS:The RESHAPE-HF2 study is an investigator-initiated, prospective, randomized, multicentre trial including patients with symptomatic HF, a left ventricular ejection fraction (LVEF) between 20% and 50% with moderate-to-severe or severe FMR, for whom isolated mitral valve surgery was not recommended. Patients were randomized 1:1 to a strategy of delivering or withholding MitraClip. Of 506 patients randomized, the mean age of the patients was 70 ± 10 years, and 99 of them (20%) were women. The median EuroSCORE II was 5.3 (2.8-9.0) and median plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 2745 (1407-5385) pg/ml. Most patients were prescribed beta-blockers (96%), diuretics (96%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (82%) and mineralocorticoid receptor antagonists (82%). The use of sodium-glucose cotransporter 2 inhibitors was rare (7%). Cardiac resynchronization therapy (CRT) devices had been previously implanted in 29% of patients. Mean LVEF, left ventricular end-diastolic volume and effective regurgitant orifice area (EROA) were 31 ± 8%, 211 ± 76 ml and 0.25 ± 0.08 cm2, respectively, whereas 44% of patients had mitral regurgitation severity of grade 4+. Compared to patients enrolled in COAPT and MITRA-FR, those enrolled in RESHAPE-HF2 were less likely to have mitral regurgitation grade 4+ and, on average, HAD lower EROA, and plasma NT-proBNP and higher estimated glomerular filtration rate, but otherwise had similar age, comorbidities, CRT therapy and LVEF. CONCLUSION:Patients enrolled in RESHAPE-HF2 represent a third distinct population where MitraClip was tested in, that is one mainly comprising of patients with moderate-to-severe FMR instead of only severe FMR, as enrolled in the COAPT and MITRA-FR trials. The results of RESHAPE-HF2 will provide crucial insights regarding broader application of the transcatheter edge-to-edge repair procedure in clinical practice.

Importance Healthcare concepts for chronic diseases based on tele-monitoring have become increasingly important during COVID-19 pandemic. Objective To study the effectiveness of a novel integrated care concept (NICC) that combines tele-monitoring with the support of a call centre in addition to guideline therapy for patients with atrial fibrillation, heart failure, or treatment-resistant hypertension. Design A prospective, parallel-group, open-label, randomized, controlled trial. Setting Between December 2017 and August 2019 at the Rostock University Medical Center (Germany). Participants Including 960 patients with either atrial fibrillation, heart failure, or treatment-resistant hypertension. Interventions Patients were randomized to either NICC ( n = 478) or standard-of-care (SoC) ( n = 482) in a 1:1 ratio. Patients in the NICC group received a combination of tele-monitoring and intensive follow-up and care through a call centre. Main outcomes and measures Three primary endpoints were formulated: (1) composite of all-cause mortality, stroke, and myocardial infarction; (2) number of inpatient days; (3) the first plus cardiac decompensation, all measured at 12-months follow-up. Superiority was evaluated using a hierarchical multiple testing strategy for the 3 primary endpoints, where the first step is to test the second primary endpoint (hospitalization) at two-sided 5%-significance level. In case of a non-significant difference between the groups for the rate of hospitalization, the superiority of NICC over SoC is not shown. Results The first primary endpoint occurred in 1.5% of NICC and 5.2% of SoC patients (OR: 3.3 [95%CI 1.4–8.3], p = 0.009). The number of inpatient treatment days did not differ significantly between both groups ( p = 0.122). The third primary endpoint occurred in 3.6% of NICC and 8.1% of SoC patients (OR: 2.2 [95%CI 1.2–4.2], p = 0.016). Four patients died of all-cause death in the NICC and 23 in the SoC groups (OR: 4.4 [95%CI 1.6–12.6], p = 0.006). Based on the prespecified hierarchical statistical analysis protocol for multiple testing, the trial did not meet its primary outcome measure. Conclusions and relevance Among patients with atrial fibrillation, heart failure, or treatment-resistant hypertension, the NICC approach was not superior over SoC, despite a significant reduction in all-cause mortality, stroke, myocardial infarction and cardiac decompensation. Trial registration ClinicalTrials.gov Identifier: NCT03317951.

ObjectivesThe main aim of this work was to analyse the cost-effectiveness of an integrated care concept (NICC) that combines telemonitoring with the support of a care centre in addition to guideline therapy for patients. Secondary aims were to compare health utility and health-related quality of life (QoL) between NICC and standard of care (SoC).MethodsThe randomised controlled CardioCare MV Trial compared NICC and SoC in patients from Mecklenburg-West Pomerania (Germany) with atrial fibrillation, heart failure or treatment-resistant hypertension. QoL was measured using the EQ-5D-5L at baseline, 6 months and 1 year follow-up. Quality-adjusted life years (QALYs), EQ5D utility scores, Visual Analogue Scale (VAS) Scores and VAS adjusted life years (VAS-AL) were calculated. Cost data were obtained from health insurance companies, and the payer perspective was taken in health economic analyses. Quantile regression was used with adjustments for stratification variables.ResultsThe net benefit of NICC (QALY) was 0.031 (95% CI 0.012 to 0.050; p=0.001) in this trial involving 957 patients. EQ5D Index values, VAS-ALs and VAS were larger for NICC compared with SoC at 1 year follow-up (all p≤0.004). Direct cost per patient and year were €323 (CI €157 to €489) lower in the NICC group. When 2000 patients are served by the care centre, NICC is cost-effective if one is willing to pay €10 652 per QALY per year.ConclusionNICC was associated with higher QoL and health utility. The programme is cost-effective if one is willing to pay approximately €11 000 per QALY per year.

Biofluid mechanics play an important role in the study of the mechanism of cardiovascular diseases and in the development of new implants. For the assessment of hydrodynamic parameters, experimental methods as well as in-silico approaches can be used, such as particle image velocimetry (PIV) and Deep Learning, respectively. Challenges for PIV are the optical access to the region of interest, and time consumption for measuring and post-processing analysis in particular for three dimensional flow. To overcome these limitations state-of-the-art deep learning algorithms could be utilized to augment spatially coarse resolved flow fields. In this study, we demonstrate the use of Physics Informed Neural Networks (PINN) to augment PIV measurement data. To demonstrate a combined workflow, we investigate the flow of a Newtonian fluid through a simplified aneurysm under laminar conditions. Generation of synthetic PIV particle images of a single measurement plane and the corresponding PIV vector calculations were performed as the basis for the PINN algorithm. Based on the Navier-Stokes equations the PINN reconstructs the entire 3D flow field and pressure distribution inside the aneurysm. We observed qualitative agreements between ground through data and PINN predictions. Nevertheless, there are substantial differences in the quantitative, locally resolved comparison of the flow metrics, despite the generally tendency for the PINN algorithm to correctly augment the flow field.

Severe aortic valve stenosis has been successfully treated with minimally invasive transcatheter aortic valve replacement (TAVR) for more than 20 years. The therapy is applied to an increasing cohort of patients. Nevertheless, paravalvular leakage (PVL) remains one of the main complications after TAVR implantation reducing safety and efficacy of the implant. To improve TAVR performance, virtual patient cohorts can be used to generate a significant amount of data with biologically varying conditions comparable to clinically realworld data. For this purpose, in silico models need to be established which are used to evaluate the possible occurrence of PVL. When establishing in silico models, the question between simplification to reduce computational effort and still valid information from the model must always be clarified. Thus, we investigated the comparability between steadystate and transient PVL measurements as an input parameter for simulations in virtual cohorts. A clinically established TAVR was implanted into different annulus models and tested in a steady-state back-flow test bench and in a pulse duplicator system. As a result, leakage rates were compared and assumptions for the in silico models were derived. Although the trend of PVL is comparable in steady-state and transient conditions, absolute values differ making it difficult to extract generalized assumptions. Especially when PVL increased, e.g. in a larger implantation diameter or in an imperfect annulus, the variation also increased up to 50% of the measured value.