Five-year follow-up of the endothelial progenitor cell capturing stent versus the paxlitaxel-eluting stent in de novo coronary lesions with a high risk of coronary restenosis.

OBJECTIVES: To assess the long-term safety and clinical efficacy of the Genous endothelial progenitor cell capturing stent (ECS) compared with the TAXUS Liberté paclitaxel-eluting stent (PES) in lesions with a high risk of restenosis. BACKGROUND: Instead of the use of cytotoxic or cytostatic drugs in drug-eluting stents, a "pro-healing" approach in ECS may overcome impeded healing response due to delayed functional endothelialization of the stent struts. METHODS: In the prospective, randomized TRIAS pilot study 193 patients with coronary artery lesions carrying a high risk of restenosis were included (ECS: n = 98, PES: n = 95). The primary focus of this analysis was target vessel failure (TVF) at 5 years. Dual antiplatelet therapy was prescribed for ≥1 month after ECS and for ≥6 months after PES. RESULTS: At 5 years follow-up, no significant differences were found in TVF (ECS 24% vs. PES 29%, risk difference 95% confidence interval (RDCI) -17.3% to 7.4%). Between 2 and 5 years after the index procedure, low numbers of TVF were observed in ECS compared with PES (ECS 4% vs. PES 16%, RDCI -20.8% to -2.3%). There was no definite stent thrombosis in ECS compared with four patients in the PES group. CONCLUSION: This is the first randomized study providing very long-term clinical efficacy and safety of the ECS in lesions carrying a high risk of restenosis. At 5 years follow-up, TVF rates in ECS group are numerically lower compared with PES due to an increase of events between 2 and 5 years after the index procedure.

Feasibility and safety of early discharge after transfemoral transcatheter aortic valve implantation - rationale and design of the FAST-TAVI registry.

BACKGROUND: There is an increasing trend towards shorter hospital stays after transcatheter aortic valve implantation (TAVI), in particular for patients undergoing the procedure via transfemoral (TF) access. Preliminary data suggest that there exists a population of patients that can be discharged safely very early after TF-TAVI. However, current evidence is limited to few retrospective studies, encompassing relatively small sample sizes. METHODS: The Feasibility And Safety of early discharge after Transfemoral TAVI (FAST-TAVI) registry is a prospective observational registry that will be conducted at 10 sites across Italy, the Netherlands and the UK. Patients will be included if they have been scheduled to undergo TF-TAVI with the balloon-expandable SAPIEN 3 transcatheter heart valve (THV; Edwards Lifesciences, Irvine, CA). The primary endpoint is a composite of all-cause mortality, vascular-access-related complications, permanent pacemaker implantation, stroke, re-hospitalisation due to cardiac reasons, kidney failure and major bleeding, occurring during the first 30 days after hospital discharge. Patients will be stratified according to whether they were high or low risk for early discharge (≤3 days) (following pre-specified criteria), and according to whether or not they were discharged early. Secondary endpoints will include time-to-event (Kaplan-Meier) analysis for the primary outcome and its individual components, analysis of the relative costs of early and late discharge, and changes in short- and long-term quality of life. Multivariate logistic regression will be used to identify factors that indicate that a patient may be suitable for early discharge. DISCUSSION: The data gathered in the FAST-TAVI registry should help to clarify the safety of early discharge after TF-TAVI and to identify patient and procedural characteristics that make early discharge from hospital a safe and cost-effective strategy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02404467 (registration first received March 23rd 2015).

Older coronary thrombus is an independent predictor of 1-year mortality in acute myocardial infarction.

BACKGROUND: We have previously shown that older thrombus is associated with a twofold higher long-term mortality in ST-segment elevation myocardial infarction (STEMI) patients after primary percutaneous coronary intervention (pPCI). We evaluated whether the addition of the presence of older thrombus to a multimarker model would result in increased predictive power for 1-year mortality in STEMI patients. METHODS: The study population (n = 1442) consists of STEMI patients treated with thrombus aspiration during pPCI. Patients were included if aspirated thrombus material could histopathologically be classified according to thrombus age (n = 870) and laboratory measurements of biomarkers (cardiac troponin T, glucose, N-terminal pro-brain natriuretic peptide, estimated glomerular filtration rate and C-reactive protein) were available. The additional prognostic value of the presence of older thrombus beyond multiple biomarkers and established clinical risk factors was evaluated using multivariate Cox regression models. RESULTS: Serum biomarker concentrations were similar between patients with fresh and older thrombus. Sixty patients (7%) died within 1 year. The presence of older thrombus remained strongly associated with mortality at 1 year after multivariable adjustment for multiple biomarkers and established clinical risk factors. Addition of older thrombus to either a model including clinical risk factors and biomarkers or a model including solely biomarkers resulted in significant increases in the discriminative value, evidenced by net reclassification improvement and integrated discriminative improvement. CONCLUSIONS: The presence of older thrombus provides independent complementary information to a multimarker model including established clinical risk factors and multiple biomarkers for predicting 1-year mortality in STEMI patients treated with pPCI and thrombus aspiration.

Influence of chronic kidney disease on anticoagulation levels and bleeding after primary percutaneous coronary intervention in patients treated with unfractionated heparin.

Unfractionated heparin (UFH) plasma protein binding and elimination might be impaired in patients with chronic kidney disease (CKD-defined as creatinine clearance <60 ml/min). It is currently unknown at which UFH bolus dose persistent prolongation of activated partial thromboplastin time (aPTT) occurs in ST-segment elevation myocardial infarction (STEMI) patients with CKD. We investigated the effect of different UFH bolus doses on the first aPTT measured within 6 and 12 h after PPCI in 1071 STEMI patients with and without CKD undergoing primary percutaneous coronary intervention (PPCI) between 1-1-2003 and 31-07-2008. In the first 6 h after PPCI, aPTT ratio was 5.1 for patients with CKD versus 3.4 for those without (p < 0.001). The proportion of patients with markedly high aPTTs (aPTT ratio ≥ 4 times control) increased with increasing heparin bolus and beyond 130 IU/kg there was a marked difference between patients with and without CKD (74.1 and 42.3 % respectively, p < 0.001). By multivariable analysis, CKD was associated with an increased risk of markedly high aPTTs (odds ratio (OR) 2.04; 95 % confidence interval (CI) 1.27-3.27), driven largely by an increased risk of aPTT prolongation in patients treated with UFH boluses ≥130 IU/kg (OR 3.69; 95 % CI 1.85-7.36; p for interaction = 0.009). In conclusion, CKD is associated with severe persistent aPTT prolongation in STEMI patients undergoing PPCI, possibly due to impaired plasma protein binding and reduced UFH elimination. A lower heparin bolus dose might result in lower aPTTs and less bleeding complications in patients with CKD undergoing PPCI.

Long-term ischaemic and bleeding outcomes after primary percutaneous coronary intervention for ST-elevation myocardial infarction in the elderly.

BACKGROUND: The population is ageing rapidly and the proportion of patients aged ≥ 80 years undergoing primary percutaneous coronary intervention (PCI) is rising, but clinical trials have primarily been performed in younger patients. METHODS: Patients undergoing primary PCI between 2003 and 2008 were subdivided into 3 groups: < 60, 60-79, and ≥ 80 years. Endpoints at 3-year follow-up included all-cause mortality, recurrent myocardial infarction (reMI), stent thrombosis, target lesion revascularisation (TLR), bleeding (BARC bleeding ≥ 3), stroke, and major adverse cardiovascular events (MACE, a composite of cardiac mortality, reMI, stroke and TLR). RESULTS: 2002 patients with ST-segment elevation myocardial infarction (STEMI) were included, 885 (44.2 %) aged < 60, 921 (46.0 %) 60-79, and 196 (9.7 %) ≥ 80 years. Comorbidities such as diabetes mellitus, prior stroke, malignant disease, anaemia, and chronic kidney disease were more prevalent in patients ≥ 80 years. The incidence of both ischaemic and bleeding events strongly increased with age. Age ≥ 80 years was an independent predictor of mortality (HR 2.56, 95 % CI1.69-3.87, p < 0.001), a borderline non-significant predictor of overall bleeding (HR 1.38, 95 %CI 0.95-2.00, p = 0.088), and a significant predictor of non-access site bleeding (HR 2.26, 95 %CI 1.46-3.51, p < 0.001). CONCLUSION: Patients ≥ 80 years experienced high rates of ischaemic and bleeding complications; especially in this high-risk patient group individualised therapy is needed to optimise clinical outcomes.

Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial.

BACKGROUND: If percutaneous coronary intervention (PCI) is required in patients taking oral anticoagulants, antiplatelet therapy with aspirin and clopidogrel is indicated, but such triple therapy increases the risk of serious bleeding. We investigated the safety and efficacy of clopidogrel alone compared with clopidogrel plus aspirin. METHODS: We did an open-label, multicentre, randomised, controlled trial in 15 centres in Belgium and the Netherlands. From November, 2008, to November, 2011, adults receiving oral anticoagulants and undergoing PCI were assigned clopidogrel alone (double therapy) or clopidogrel plus aspirin (triple therapy). The primary outcome was any bleeding episode within 1 year of PCI, assessed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00769938. FINDINGS: 573 patients were enrolled and 1-year data were available for 279 (98·2%) patients assigned double therapy and 284 (98·3%) assigned triple therapy. Mean ages were 70·3 (SD 7·0) years and 69·5 (8·0) years, respectively. Bleeding episodes were seen in 54 (19·4%) patients receiving double therapy and in 126 (44·4%) receiving triple therapy (hazard ratio [HR] 0·36, 95% CI 0·26-0·50, p<0·0001). In the double-therapy group, six (2·2%) patients had multiple bleeding events, compared with 34 (12·0%) in the triple-therapy group. 11 (3·9%) patients receiving double therapy required at least one blood transfusion, compared with 27 (9·5%) patients in the triple-therapy group (odds ratio from Kaplan-Meier curve 0·39, 95% CI 0·17-0·84, p=0·011). INTERPRETATION: Use of clopiogrel without aspirin was associated with a significant reduction in bleeding complications and no increase in the rate of thrombotic events. FUNDING: Antonius Ziekenhuis Foundation, Strect Foundation.

Amsterdam Investigator-initiateD Absorb strategy all-comers trial (AIDA trial): a clinical evaluation comparing the efficacy and performance of ABSORB everolimus-eluting bioresorbable vascular scaffold strategy vs the XIENCE family (XIENCE PRIME or XIENCE Xpedition) everolimus-eluting coronary stent strategy in the treatment of coronary lesions in consecutive all-comers: rationale and study design.

BACKGROUND: The Absorb everolimus-eluting bioresorbable vascular scaffold (AbsorbBVS) is a completely resorbable device engineered to overcome the limitations of permanent metallic stents, providing temporary scaffolding and antiproliferative drug delivery for the treatment of obstructive coronary artery disease. METHODS: The objective of the AIDA trial is to evaluate the efficacy and performance in an contemporary all-comer population of the AbsorbBVS strategy vs the XIENCE family everolimus-eluting metallic coronary stent system in the treatment of coronary lesions. The AIDA trial is a prospective, randomized (1:1), active-control, single-blinded, all-comer, noninferiority trial. A total of 2,690 subjects will be enrolled with broad inclusion and limited exclusion criteria according to the "Instructions for Use" of the AbsorbBVS strategy. The study population includes both simple and complex lesions, in patients with stable and acute coronary syndrome. The follow-up continues for 5years. The primary end point of the trial is target vessel failure, defined as the composite of cardiac death, myocardial infarction, and target vessel revascularization, at 2years. This study is registered on ClinicalTrials.gov with number NCT01858077. CONCLUSION: The AIDA trial will provide the first randomized direct comparison between the everolimus-eluting bioresorbable vascular scaffold and the everolimus-eluting metallic stent in contemporary percutaneous coronary intervention practice.

Higher Edmonton Frail Scale prior to transcatheter Aortic Valve Implantation is related to longer hospital stay and mortality.

BACKGROUND: International guidelines for the management of valvular heart disease recommend frailty assessment prior to Transcatheter Aortic Valve Implantation (TAVI), however there is no consensus how to assess frailty. We investigated whether frailty status assessed with the Edmonton Frail Scale (EFS, range 0-17 points) relates to length of stay (LOS), short- and long-term mortality and adverse outcomes after TAVI. METHODS: In this study we included 357 patients between April 2016 till December 2018. EFS was assessed at baseline. Patients were classified into low (0-3), intermediate (4-7) or high frailty status (8-17). LOS was defined as the number of days between admission and discharge. Mortality data were obtained up to four years after TAVI. Adverse events were defined by Valve Academic Research Consortium (VARC)-2 criteria and collected <30 days after TAVI. RESULTS: Patients with higher frailty status had longer median LOS (days (IQR): low 5 (3), intermediate 6 (4) and high 7 (5), p < 0.001) and higher mortality: low vs intermediate vs high at 30 days 0.5%, 2.2%, 7.0% (p = 0.050), 1 year 3.7%, 10.0%, 15.2% (p = 0.052), 2 years 9.2%, 17.8%, 31.7% (p = 0.003), 3 years 17.2%, 24.0, 47.0% (p = 0.001) and 4 years 19.6%, 30.8%, 55.6% (p < 0.001). Frail patients received more often a pacemaker (2.6%, 6.6%, 13.5%, p = 0.048). CONCLUSION: In clinical practice, the EFS is a useful tool to screen for frailty in TAVI patients. This tool may possibly be expanded to determine benefit versus harm-risk in these patients and whether specific pre-procedurally interventions are needed in order to reduce mortality.

Detecting aortic valve stenosis based on the non-invasive blood pressure waveform-a proof of concept study.

The incidence of aortic valve stenosis (AoS) increases with age, and once diagnosed, symptomatic severe AoS has a yearly mortality rate of 25%. AoS is diagnosed with transthoracic echocardiography (TTE), however, this gold standard is time consuming and operator and acoustic window dependent. As AoS affects the arterial blood pressure waveform, AoS-specific waveform features might serve as a diagnostic tool. Aim of the present study was to develop a novel, non-invasive, AoS detection model based on blood pressures waveforms. This cross-sectional study included patients with AoS undergoing elective transcatheter or surgical aortic valve replacement. AoS was determined using TTE, and patients with no or mild AoS were labelled as patients without AoS, while patients with moderate or severe AoS were labelled as patients with AoS. Non-invasive blood pressure measurements were performed in awake patients. Ten minutes of consecutive data was collected. Several blood pressure-based features were derived, and the median, interquartile range, variance, and the 1st and 9th decile of the change of these features were calculated. The primary outcome was the development of a machine-learning model for AoS detection, investigating multiple classifiers and training on the area under the receiver-operating curve (AUROC). In total, 101 patients with AoS and 48 patients without AoS were included. Patients with AoS showed an increase in left ventricular ejection time (0.02 s, p = 0.001), a delayed maximum upstroke in the systolic phase (0.015 s, p < 0.001), and a delayed maximal systolic pressure (0.03 s, p < 0.001) compared to patients without AoS. With the logistic regression model, a sensitivity of 0.81, specificity of 0.67, and AUROC of 0.79 were found. The majority of the population without AoS was male (85%), whereas in the population with AoS this was evenly distributed (54% males). Age was significantly (5 years, p < 0.001) higher in the population with AoS. In the present study, we developed a novel model able to distinguish no to mild AoS from moderate to severe AoS, based on blood pressure features with high accuracy. Clinical registration number: The study entailing patients with TAVR treatment was registered at ClinicalTrials.gov (NCT03088787, https://clinicaltrials.gov/ct2/show/NCT03088787 ). The study with elective cardiac surgery patients was registered with the Netherland Trial Register (NL7810, https://trialsearch.who.int/Trial2.aspx?TrialID=NL7810 ).

Low muscle quality on a procedural computed tomography scan assessed with deep learning as a practical useful predictor of mortality in patients with severe aortic valve stenosis.

BACKGROUND & AIMS: Accurate diagnosis of sarcopenia requires evaluation of muscle quality, which refers to the amount of fat infiltration in muscle tissue. In this study, we aim to investigate whether we can independently predict mortality risk in transcatheter aortic valve implantation (TAVI) patients, using automatic deep learning algorithms to assess muscle quality on procedural computed tomography (CT) scans. METHODS: This study included 1199 patients with severe aortic stenosis who underwent transcatheter aortic valve implantation (TAVI) between January 2010 and January 2020. A procedural CT scan was performed as part of the preprocedural-TAVI evaluation, and the scans were analyzed using deep-learning-based software to automatically determine skeletal muscle density (SMD) and intermuscular adipose tissue (IMAT). The association of SMD and IMAT with all-cause mortality was analyzed using a Cox regression model, adjusted for other known mortality predictors, including muscle mass. RESULTS: The mean age of the participants was 80 ± 7 years, 53% were female. The median observation time was 1084 days, and the overall mortality rate was 39%. We found that the lowest tertile of muscle quality, as determined by SMD, was associated with an increased risk of mortality (HR 1.40 [95%CI: 1.15-1.70], p < 0.01). Similarly, low muscle quality as defined by high IMAT in the lowest tertile was also associated with increased mortality risk (HR 1.24 [95%CI: 1.01-1.52], p = 0.04). CONCLUSIONS: Our findings suggest that deep learning-assessed low muscle quality, as indicated by fat infiltration in muscle tissue, is a practical, useful and independent predictor of mortality after TAVI.

Adjunctive thrombus aspiration versus conventional percutaneous coronary intervention in ST-elevation myocardial infarction.

OBJECTIVES: The objective of this analysis is to determine the effects on mortality of thrombus aspiration during primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) compared with conventional PCI. BACKGROUND: Adjunctive thrombus aspiration in STEMI improves markers of myocardial reperfusion but evidence for improved survival is limited to the TAPAS trial. METHODS: We used data of 3,750 consecutive STEMI patients treated with either conventional PCI or thrombus aspiration between August 1, 2001 and January 1, 2009. For each patient, a propensity score was calculated based on clinical and angiographic characteristics, predicting a patient's probability of having been treated with thrombus aspiration. This propensity score was used in several ways to account for differences between patients treated with and without thrombus aspiration. In our primary analysis, patients treated with thrombus aspiration were matched one-to-one with patients treated with conventional PCI on their propensity score (1,391 matched pairs). Kaplan Meier and Cox regression models were used to estimate the influence of treatment on one-year mortality. RESULTS: In total, 1,502 patients (40.1%) were treated with thrombus aspiration. In the propensity matched cohort, after one year 7.2% of patients treated with thrombus aspiration had died compared with 9.3% of patients in the control group. The hazard ratio for one-year mortality in patients treated with thrombus aspiration was 0.76 (95% CI: 0.59-0.99; P = 0.043). The hazard ratio remained materially unaltered and statistically significant in secondary analyses, varying between 0.61 and 0.77. CONCLUSION: The routine use of thrombus aspiration was associated with reduced one-year mortality in this large real-world patient cohort. These data support the observed survival benefit in the TAPAS trial.

Clinical outcomes after bare-metal stenting in diabetic patients with lesions carrying a low risk of restenosis.

OBJECTIVE: To evaluate the clinical results of diabetic patients undergoing percutaneous coronary intervention (PCI) for coronary artery lesions carrying a low risk of restenosis treated with a bare-metal stent (BMS). BACKGROUND: There is a discrepancy between current international guidelines on the use of BMS in diabetics with low risk of restenosis coronary artery lesions. METHODS AND RESULTS: Registry data from diabetic patients who underwent non-urgent PCI in a high-volume tertiary referral hospital in the Netherlands was used. The main outcomes were target lesion revascularization (TLR) and the composite of cardiac death, myocardial infarction, and target vessel revascularization at 1-year of follow-up. A total of 1,951 patients were included, of which 1,596 non-diabetics (non-DM), 231 non-insulin requiring diabetics (NIRDM), and 124 insulin requiring diabetics (IRDM).TLR rates in non-DM versus NIRDM were similar (6.3% vs. 5.6%; P = 0.68), whereas TLR in IRDM was higher (6.3% vs. 11.3%; P = 0.03). The composite of cardiovascular clinical outcomes was not significantly different in non-DM versus NIRDM (9.5% vs. 13.4%; P = 0.07), though in IRDM the incidence was higher (9.5% vs. 17.7%; P < 0.01). CONCLUSION: No differences were observed in TLR or composite clinical endpoint at 1-year between non-DM and NIRDM after BMS placement in coronary artery lesions carrying a low risk of restenosis. The presence of IRDM was associated with higher TLR rates when treated with BMS. These results imply that BMS placement may be considered in patients with NIRDM but further work is required to define treatment strategies and, more importantly, improve the outcomes in diabetics.

Galectin-2 expression is dependent on the rs7291467 polymorphism and acts as an inhibitor of arteriogenesis.

AIMS: In patients with obstructive coronary artery disease (CAD), the growth of collateral arteries, i.e. arteriogenesis, can preserve myocardial tissue perfusion and function. Monocytes modulate this process, supplying locally the necessary growth factors and degrading enzymes. Knowledge on factors involved in human arteriogenesis is scarce. Thus, the aim of the present study is to identify targets in monocytes that are critical for arteriogenesis in patients with CAD. METHODS AND RESULTS: A total of 50 patients with a chronic total coronary occlusion were dichotomized according to their collateral flow index. From each patient, RNA was isolated from unstimulated peripheral blood monocytes, monocytes stimulated by lipopolysaccharide (LPS) or interleukin (IL)-4, and from macrophages. Increased mRNA expression of galectin-2 was found in three out of four monocytic cell types of patients with a low capacity of the collateral circulation (P= 0.03 for unstimulated monocytes; P= 0.02 for LPS-stimulated monocytes; P= 0.20 for IL-4-stimulated monocytes; P= 0.02 for macrophages). Additionally, galectin-2 mRNA expression was significantly associated with the rs7291467 polymorphism in LGALS2 encoding galectin-2 in all four monocytic cell types. Patient with the rs7291467 CC genotype displayed highest galectin-2 expression, and also tended to have a lower arteriogenic response. To evaluate the effect of galectin-2 on arteriogenesis in vivo, we used a murine hindlimb model. Treatment with galectin-2 markedly impaired the perfusion restoration at Day 7. CONCLUSION: Collectively, these results identify galectin-2 as a novel inhibitor of arteriogenesis. Modulation of galectin-2 may constitute a new therapeutic strategy for the stimulation of arteriogenesis in patients with CAD.

An integrated approach to geographic validation helped scrutinize prediction model performance and its variability.

OBJECTIVES: To illustrate in-depth validation of prediction models developed on multicenter data. METHODS: For each hospital in a multicenter registry, we evaluated predictive performance of a 30-day mortality prediction model for transcatheter aortic valve implantation (TAVI) using the Netherlands heart registration (NHR) dataset. We measured discrimination and calibration per hospital in a leave-center-out analysis (LCOA). Meta-analysis was used to calculate I2 values per performance metric from the LCOA and to compute mean and confidence interval (CI) estimates. Case mix differences between studies were inspected using the framework of Debray et al. for understanding external validation. We also aimed to discover subgroups (SGs) with high model prediction error (PE) and their distribution over the centers. RESULTS: We studied 16 hospitals with 11,599 TAVI patients with an early mortality of 3.7%. The models' area under the curve (AUCs) had a wide range between hospitals from 0.59 to 0.79, and miscalibration occurred in seven hospitals. Mean AUC from meta-analysis was 0.68 (95% CI 0.65-0.70). I2 values were 0%, 74%, and 0% for AUC, calibration intercept and slope, respectively. Between-hospital case-mix differences were substantial, and model transportability was low. One SG was discovered with marked global PE and was associated with poor performance on validation centers. CONCLUSION: The illustrated combination of approaches provides useful insights to inspect multicenter-based prediction models, and it exposes their limitations in transportability and performance variability when applied to different populations.

Temporal validation of 30-day mortality prediction models for transcatheter aortic valve implantation using statistical process control - An observational study in a national population.

Background: Various mortality prediction models for Transcatheter Aortic Valve Implantation (TAVI) have been developed in the past years. The effect of time on the performance of such models, however, is unclear given the improvements in the procedure and changes in patient selection, potentially jeopardizing the usefulness of the prediction models in clinical practice. We aim to explore how time affects the performance and stability of different types of prediction models of 30-day mortality after TAVI. Methods: We developed both parametric (Logistic Regression) and non-parametric (XGBoost) models to predict 30-day mortality after TAVI using data from the Netherlands Heart Registration. The models were trained with data from 2013 to the beginning of 2016 and pre-control charts from Statistical Process Control were used to analyse how time affects the models' performance on independent data from the mid of 2016 to the end of 2019. The area under the Receiver Operating Characteristics curve (AUC) was used to evaluate the models in terms of discrimination and the Brier Score (BS), which is related to calibration, in terms of accuracy of the predicted probabilities. To understand the extent to which refitting the models contribute to the models' stability, we also allowed the models to be updated over time. Results: We included data from 11,291 consecutive TAVI patients from hospitals in the Netherlands. The parametric model without re-training had a median AUC of 0.64 (IQR 0.54-0.73) and BS of 0.028 (IQR 0.021-0.035). For the non-parametric model, the median AUC was 0.63 (IQR 0.48-0.68) and BS was 0.027 (IQR 0.021-0.036). Over time, the developed parametric model was stable in terms of AUC and unstable in terms of BS. The non-parametric model was considered unstable in both AUC and BS. Repeated model refitting resulted in stable models in terms of AUC and decreased the variability of BS, although BS was still unstable. The refitted parametric model had a median AUC of 0.66 (IQR 0.57-0.73) and BS of 0.027 (IQR 0.020-0.035) while the non-parametric model had a median AUC of 0.66 (IQR 0.57-0.74) and BS of 0.027 (IQR 0.023-0.035). Conclusions: The temporal validation of the TAVI 30-day mortality prediction models showed that the models refitted over time are more stable and accurate when compared to the frozen models. This highlights the importance of repeatedly refitted models over time to improve or at least maintain their performance stability. The non-parametric approach did not show improvement over the parametric approach.

Evaluation of a Fully Automatic Deep Learning-Based Method for the Measurement of Psoas Muscle Area.

Background: Manual muscle mass assessment based on Computed Tomography (CT) scans is recognized as a good marker for malnutrition, sarcopenia, and adverse outcomes. However, manual muscle mass analysis is cumbersome and time consuming. An accurate fully automated method is needed. In this study, we evaluate if manual psoas annotation can be substituted by a fully automatic deep learning-based method. Methods: This study included a cohort of 583 patients with severe aortic valve stenosis planned to undergo Transcatheter Aortic Valve Replacement (TAVR). Psoas muscle area was annotated manually on the CT scan at the height of lumbar vertebra 3 (L3). The deep learning-based method mimics this approach by first determining the L3 level and subsequently segmenting the psoas at that level. The fully automatic approach was evaluated as well as segmentation and slice selection, using average bias 95% limits of agreement, Intraclass Correlation Coefficient (ICC) and within-subject Coefficient of Variation (CV). To evaluate performance of the slice selection visual inspection was performed. To evaluate segmentation Dice index was computed between the manual and automatic segmentations (0 = no overlap, 1 = perfect overlap). Results: Included patients had a mean age of 81 ± 6 and 45% was female. The fully automatic method showed a bias and limits of agreement of -0.69 [-6.60 to 5.23] cm2, an ICC of 0.78 [95% CI: 0.74-0.82] and a within-subject CV of 11.2% [95% CI: 10.2-12.2]. For slice selection, 84% of the selections were on the same vertebra between methods, bias and limits of agreement was 3.4 [-24.5 to 31.4] mm. The Dice index for segmentation was 0.93 ± 0.04, bias and limits of agreement was -0.55 [1.71-2.80] cm2. Conclusion: Fully automatic assessment of psoas muscle area demonstrates accurate performance at the L3 level in CT images. It is a reliable tool that offers great opportunities for analysis in large scale studies and in clinical applications.

Immediate reduction in left ventricular ejection time following TAVI is associated with improved quality of life.

Background: TAVI has shown to result in immediate and sustained hemodynamic alterations and improvement in health-related quality of life (HRQoL), but previous studies have been suboptimal to predict who might benefit from TAVI. The relationship between immediate hemodynamic changes and outcome has not been studied before. This study sought to assess whether an immediate hemodynamic change, reflecting myocardial contractile reserve, following TAVI is associated with improved HRQoL. Furthermore, it assessed whether pre-procedural cardiac power index (CPI) and left ventricular ejection fraction (LVEF) could predict these changes. Methods: During the TAVI procedure, blood pressure and systemic hemodynamics were prospectively collected with a Nexfin® non-invasive monitor. HRQoL was evaluated pre-procedurally and 12 weeks after the procedure, using the EQ-5D-5L classification tool. Results: Overall, 97/114 (85%) of the included patients were eligible for analyses. Systolic, diastolic and mean arterial pressure, heart rate, and stroke volume increased immediately after TAVI (all p < 0.005), and left ventricular ejection time (LVET) immediately decreased with 10 ms (95%CI = -4 to -16, p < 0.001). Overall HRQoLindex increased from 0.810 [0.662-0.914] before to 0.887 [0.718-0.953] after TAVI (p = 0.016). An immediate decrease in LVET was associated with an increase in HRQoLindex (0.02 index points per 10 ms LVET decrease, p = 0.041). Pre-procedural CPI and LVEF did not predict hemodynamic changes or change in HRQoL. Conclusion: TAVI resulted in an immediate hemodynamic response and increase in HRQoL. Immediate reduction in LVET, suggesting unloading of the ventricle, was associated with an increase in HRQoL, but neither pre-procedural CPI nor LVEF predicted these changes. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03088787.

The Impella 2.5 and 5.0 devices for ST-elevation myocardial infarction patients presenting with severe and profound cardiogenic shock: the Academic Medical Center intensive care unit experience.

OBJECTIVE: Cardiogenic shock remains an important therapeutic challenge, with high in-hospital mortality rates. Mechanical circulatory support may be beneficial in these patients. Since the efficacy of the intra-aortic balloon pump seems limited, new percutaneously placed mechanical left ventricular support devices, such as the Impella system, have been developed for this purpose. Our current purpose was to describe our experience with the Impella system in patients with ST-elevation myocardial infarction presenting in profound cardiogenic shock, who were admitted to our intensive care unit for mechanical ventilation. METHODS: From January 2004 through August 2010, a total of 34 ST-elevation myocardial infarction patients with profound cardiogenic shock were admitted to our intensive care unit and treated with either the Impella 2.5 or the Impella 5.0 device. Baseline and follow-up characteristics were collected retrospectively. MEASUREMENTS AND MAIN RESULTS: Within the study cohort, 25 patients initially received treatment with the Impella 2.5, whereas nine patients received immediate Impella 5.0 support. Eight out of 25 patients in the Impella 2.5 group were upgraded to 5.0 support. After 48 hrs, 14 of 25 patients in the 2.5 group were alive, five of whom had been upgraded. In the 5.0 group, eight out of nine patients were alive. After 30 days, six of 25 patients in the 2.5 group were alive, three of whom had been upgraded. In the 5.0 group, three of nine patients were alive at 30 days. CONCLUSIONS: In ST-elevation myocardial infarction patients with severe and profound cardiogenic shock, our initial experience suggests improved survival in patients who received immediate Impella 5.0 treatment, as well as in patients who were upgraded from 2.5 to 5.0 support, when compared to patients who received only Impella 2.5 support.

Two-year follow-up of the Genous™ endothelial progenitor cell capturing stent versus the Taxus Liberté stent in patients with de novo coronary artery lesions with a high-risk of restenosis: a randomized, single-center, pilot study.

BACKGROUND: In the prospective randomized TRIAS pilot study, the bio-engineered Genous™ endothelial progenitor cell capturing stent was compared with the Taxus Liberté™ SR paclitaxel-eluting stent. At 1 yr, a statistically nonsignificant difference in the rates of target vessel failure (cardiac death, myocardial infarction, or target vessel revascularization) was observed. We have evaluated the safety and efficacy up to 2 yr. METHODS: A total of 193 patients with de novo coronary artery lesions carrying a high risk of restenosis were randomized to a Genous stent versus a Taxus stent. Dual antiplatelet therapy was prescribed for ≥1 month after Genous stent implantation and for ≥6 months after a Taxus stent. RESULTS: Between 1 and 2 yr, patients treated with the Genous stent tended to have fewer episodes of target lesion revascularization (2.0% versus 5.3%), but nearly similar rates of cardiac death (1.0% versus 0%), myocardial infarction (0% versus 1.1%), and stent thrombosis (0% versus 1.1%) when compared with the Taxus stent. As a result, at 2-yr follow-up treatment with the Genous stent compared with the Taxus stent resulted in a nonsignificant difference in target vessel failure (TVR) (20.4% versus 15.8%; risk difference 4.6%, 95% CI -6.2-15.5%). No stent thrombosis was observed in the Genous group compared to five cases (in four patients) in the Taxus group, resulting in a difference as compared with the Taxus stent (risk difference -4.2%; 95%CI -8.2% to -0.2%). CONCLUSIONS: In the TRIAS pilot study, treatment of coronary artery lesions carrying a high risk of restenosis with the Genous compared with the Taxus stent resulted in a nonsignificant difference of TVR at 2-yr follow-up, with convergence of the Kaplan-Meier curves between 1 and 2 yr. Stent thrombosis was only observed after Taxus stent implantation.

Histopathology of aspirated thrombus and its association with ST-segment recovery in patients undergoing primary percutaneous coronary intervention with routine thrombus aspiration.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) with thrombus aspiration, the histopathology of aspirated thrombus was previously related to long-term mortality. In this study, we sought to investigate the association between histopathology of aspirated thrombus and ST-segment recovery, a marker of microvascular dysfunction, immediately at the end of the PCI procedure. METHODS: We included 892 STEMI patients who underwent primary PCI with routine thrombus aspiration and for whom combined data on histopathology of aspirated thrombus and ST-segment recovery were available. Patients were categorized according to histopathology of aspirated thrombus: fresh only (<1 day), older (>1 day), or no material aspirated. ST-segment recovery was defined as incomplete if <50%. RESULTS: Incomplete ST-segment recovery occurred in 134 of 363 patients (37%) with fresh thrombus, in 104 of 238 patients (44%) with older thrombus, and in 142 of 291 patients (49%) with no material. Unadjusted odds ratios for incomplete ST-segment recovery of patients with older thrombus and no material, when compared with patients with fresh thrombus, were 1.33 (95% CI, 0.95-1.85; P = 0.097) and 1.63 (95% CI 1.19-2.23; P = 0.002), respectively. Both associations were unchanged after multivariable adjustment for clinical predictors of ST-segment recovery. ST-segment recovery was a strong predictor of long-term mortality, independent of the histopathology of aspirated thrombus. CONCLUSIONS: This study shows that ST-segment recovery immediately at the end of the PCI procedure was a significant prognosticator, independent of the histopathology of aspirated thrombus. We found that the histopathology of aspirated thrombus (fresh, older, no material) was associated with ST-segment recovery in STEMI patients undergoing primary PCI with thrombus aspiration.