Revascularization in Ischemic Heart Failure with Reduced Left Ventricular Ejection Fraction.

PURPOSE OF REVIEW: Coronary artery disease (CAD) is estimated to account for over 60% of heart failure (HF) patients and is associated with worse outcomes than a non-ischemic etiology. In patients with ischemic HF, myocardial revascularization has multiple mechanisms of action based on the concept that blood flow restoration of viable but underperfused myocardium might reverse the hibernation of the left ventricle and prevent future spontaneous myocardial infarction, which could potentially improve patients' outcomes. Here, we aim to elaborate on indications, timing, type, and impact of completeness of revascularization in patients with heart failure with reduced ejection fraction (HFrEF) and ischemic etiology. RECENT FINDINGS: For decades, coronary artery bypass graft surgery has been the pilar of revascularization in patents with multivessel CAD and reduced EF. Recent development in the interventional field led to overall increase of percutaneous coronary intervention (PCI) adoption in treatment of ischemic HFrEF. However, recently published randomized study demonstrated no added benefit of PCI over optimal medical therapy in patients with severe ischemic cardiomyopathy challenging the beneficial role of revascularization in this setting. Since the decision on revascularization in ischemic cardiomyopathy frequently cannot be made based strictly on guidelines, tailored treatment strategy should be mandated with the essential role of multidisciplinary approach. These decisions should be based on capability to achieve complete revascularization, with the consideration that in certain situations it may not be accomplished.

Nanospheres encapsulated everolimus delivery into arterial wall-the tissue pharmacokinetics and vascular response experimental study.

OBJECTIVE: This study aimed to evaluate the pharmacokinetic profile and tissue effects of everolimus delivered into arterial wall using biodegradable nanospheres. BACKGROUND: Delivery of everolimus into the arterial wall is challenging due to its low-lipophilic profile. METHODS: A pharmacokinetic study included 28 porcine coronary arterial segments initially injured with balloon angioplasty followed by the local delivery of everolimus encapsulated in nanospheres (EEN) via injection through a microporous delivery catheter. The animals were sacrificed at 1 hour, 1,7,28, and 90-day follow-up. In the tissue effects study 16 coronary bare metal stent (BMS) were implanted following EEN delivery, 15 BMS following nanospheres delivery without the drug (reference group) and 16 implanted BMS served as a control. Angiographic and histology follow-up was scheduled at 28 and 90-day. RESULTS: The study showed high-everolimus concentrations in arterial tissue early after nanoparticles delivery followed by its gradual decrease to 1.15 ± 0.40 ng/mg at 90 days. Histology analysis showed favorable biocompatibility and healing profile with comparable area stenosis between groups at both time-points. CONCLUSIONS: The present study demonstrates for the first time the safety, biocompatibility, and long-term retention of everolimus in arterial tissue after single local delivery of biodegradable nanospheres.

Extracellular Matrix Proteomics Reveals Interplay of Aggrecan and Aggrecanases in Vascular Remodeling of Stented Coronary Arteries.

BACKGROUND: Extracellular matrix (ECM) remodeling contributes to in-stent restenosis and thrombosis. Despite its important clinical implications, little is known about ECM changes post-stent implantation. METHODS: Bare-metal and drug-eluting stents were implanted in pig coronary arteries with an overstretch under optical coherence tomography guidance. Stented segments were harvested 1, 3, 7, 14, and 28 days post-stenting for proteomics analysis of the media and neointima. RESULTS: A total of 151 ECM and ECM-associated proteins were identified by mass spectrometry. After stent implantation, proteins involved in regulating calcification were upregulated in the neointima of drug-eluting stents. The earliest changes in the media were proteins involved in inflammation and thrombosis, followed by changes in regulatory ECM proteins. By day 28, basement membrane proteins were reduced in drug-eluting stents in comparison with bare-metal stents. In contrast, the large aggregating proteoglycan aggrecan was increased. Aggrecanases of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family contribute to the catabolism of vascular proteoglycans. An increase in ADAMTS-specific aggrecan fragments was accompanied by a notable shift from ADAMTS1 and ADAMTS5 to ADAMTS4 gene expression after stent implantation. Immunostaining in human stented coronary arteries confirmed the presence of aggrecan and aggrecan fragments, in particular, at the contacts of the stent struts with the artery. Further investigation of aggrecan presence in the human vasculature revealed that aggrecan and aggrecan cleavage were more abundant in human arteries than in human veins. In addition, aggrecan synthesis was induced on grafting a vein into the arterial circulation, suggesting an important role for aggrecan in vascular plasticity. Finally, lack of ADAMTS-5 activity in mice resulted in an accumulation of aggrecan and a dilation of the thoracic aorta, confirming that aggrecanase activity regulates aggrecan abundance in the arterial wall and contributes to vascular remodeling. CONCLUSIONS: Significant differences were identified by proteomics in the ECM of coronary arteries after bare-metal and drug-eluting stent implantation, most notably an upregulation of aggrecan, a major ECM component of cartilaginous tissues that confers resistance to compression. The accumulation of aggrecan coincided with a shift in ADAMTS gene expression. This study provides the first evidence implicating aggrecan and aggrecanases in the vascular injury response after stenting.

Bioresorbable polymer-coated thin strut sirolimus-eluting stent vs durable polymer-coated everolimus-eluting stent in daily clinical practice: Propensity matched one-year results from interventional cardiology network registry.

OBJECTIVES: We sought to determine the 1-year clinical follow-up in patients treated with the thin strut (71 µm) bioabsorbable polymer-coated sirolimus-eluting stent (BP-SES) vs durable coating everolimus eluting stent (DP-EES) in daily clinical routine. BACKGROUND: Presence of durable polymers may be associated with late/very late stent thrombosis occurrence and the need for prolonged dual antiplatelet therapy. Bioabsorbable polymers may facilitate stent healing, thus enhancing clinical safety. METHODS: Interventional Cardiology Network Registry is a prospective, multicenter, observational registry of 21,400 consecutive patients treated with PCI since 2010. We analyzed 4,670 patients treated with either a BP-SES (ALEX, Balton, Poland) or DP-EES (XIENCE, Abbott, USA) with available 1-year clinical follow-up using propensity-score matching. Outcomes included target vessel revascularization (TVR) as efficacy outcome and all cause death, myocardial infarction (MI), and definite/probable stent thrombosis as safety outcomes. RESULTS: After propensity score matching, 1,649 patients treated with BP-SES and 1,649 patients treated with DP-EES were selected. Procedural and clinical characteristics were similar between both groups. There was no significant difference between tested groups in in-hospital mortality. One-year follow-up demonstrated comparable efficacy outcome, TVR (BP-SES 5.9% vs DP-EES 4.6% P = 0.45), as well as comparable safety outcomes, all cause death, MI and definite/probable stent thrombosis. CONCLUSIONS: In this multicenter registry, the BP-SES thin strut biodegradable polymer-coated sirolimus-eluting stent demonstrated comparable clinical outcomes at 1-year after implantation to the DP-EES. These data support the relative safety and efficacy of DP-SES in a broad range of patients undergoing percutaneous coronary intervention.

First in human evaluation of the vascular biocompatibility and biomechanical performance of a novel ultra high molecular weight amorphous PLLA bioresorbable scaffold in the absence of anti-proliferative drugs: Two-year imaging results in humans.

OBJECTIVES: In this first-in-human study, we prospectively studied the vascular compatibility and mechanical performance of a novel bare ultra-high molecular weight amorphous PLLA bioresorbable scaffold (BRS, FORTITUDE®, Amaranth Medical, Mountain View, California) up to two years after implantation using multimodality imaging techniques. BACKGROUND: The vascular biocompatibility of polymers used in BRS has not been fully characterized in the absence of anti-proliferative drugs. METHODS: A total of 10 patients undergoing single scaffold implantation were included in the final analysis and were followed up using optical coherence tomography (OCT) at 2-years. All devices were implanted under angiographic and intravascular ultrasound (IVUS) guidance. Angiographic and IVUS follow up was performed at 6 months. Additionally, angiography and OCT imaging were performed at 2-years. RESULTS: At 6 months, mean intra-scaffold angiographic MLD slightly decreased from baseline procedural values. However, at 2 years, mean angiographic MLD increased (post procedure; 2.9 [2.7, 3.1] mm vs. 6 months; 2.1 [1.6, 2.5] vs. 2 years; 2.4 [2.1, 2.6], P = .001). Also, angiographic percent diameter stenosis decreased and late lumen gain increased between 6 months and 2 years follow up. Mean neointimal hyperplasia volume assessed by IVUS at 6 months was 26% [15.2, 29.3]. At 2 years OCT follow up neointimal hyperplasia volume was 24.2% [19.4, 28.9]. No presence of neoatherosclerosis was identified in any of the analyzed cases. CONCLUSION: At 2 years, this novel PLLA-based BRS induced expansive vascular remodeling from 6 to 24 months, a biological phenomenon that appears to be independent of the presence of anti-proliferative drugs.

Novel ultrahigh molecular weight amorphous PLLA bioresorbable coronary scaffold upsized up to 0.8 mm beyond nominal diameter: An OCT and histopathology study in porcine coronary artery model.

OBJECTIVES: The aim of the study was to evaluate the biomechanical properties and healing pattern of novel sirolimus-eluting, ultrahigh molecular weight amorphous poly-L-lactic acid bioresorbable scaffolds (S-BRS) that have been postdilated by 0.55 and 0.8 mm beyond the nominal diameters within the pressure-diameter compliance chart range. BACKGROUND: Due to the inherent limitations of bioabsorbable polymeric materials, overexpansion/upsizing may be very limited for some BRS such as the benchmark Absorb BVS. The unique biomechanical properties of the novel S-BRS may allow it to be safely upsized. METHODS AND RESULTS: 12 coronary arteries of 4 healthy Yucatan mini-swine underwent implantation of a novel S-BRS. Upsizing by postdilation was performed up to 0.55mm (PLUS 0.55, n = 6) or 0.8 mm (PLUS 0.8, n = 6) in a manner maintaining consistent 1:1.1 stent-to-artery, thus ensuring not only the overexpansion of the scaffold but consistent level of arterial injury. Optical coherence tomography (OCT) follow-up was performed at 28 and 90-days follow-up. There was no statistical difference between the tested groups in terms of acute recoil. OCT analysis after 28 days showed numerically lower levels of neointimal formation in PLUS 0.8 compared to PLUS 0.55 group. These results were sustained at 90-days follow-up. There was no difference in late recoil between studied groups. No scaffold discontinuation, deformation or overlapping of the struts were observed. CONCLUSIONS: Overexpansion up to 0.8 mm of novel, high strength S-BRS is not associated with worse angiographic outcomes, neointimal formation or biomechanical issues such as scaffold discontinuation, deformation or overlapping of the struts, neither acutely nor chronically. © 2017 Wiley Periodicals, Inc.

Optical Coherence Tomography of De Novo Lesions and In-Stent Restenosis in Coronary Saphenous Vein Grafts (OCTOPUS Study).

BACKGROUND: The OCTOPUS registry prospectively evaluates the procedural and long-term outcomes of saphenous vein graft (SVG) PCI. The current study assessed the morphology of de novo lesions and in-stent restenosis (ISR) in patients undergoing PCI of SVG. METHODS AND RESULTS: Optical coherence tomography (OCT) of SVG lesions in consecutive patients presenting with stable CAD and ACS was carried out. Thirty-nine patients (32 de novo and 10 ISR lesions) were included in the registry. ISR occurred in 5 BMS and 5 DES. There were no differences in the presence of plaque rupture and thrombus between de novo lesions and ISR. Lipid-rich tissue was identified in both de novo lesions and in ISR (75% vs. 50%, P=0.071) with a higher prevalence in BMS than in DES (23% vs. 7.5%; P=0.048). Calcific de novo lesions were detected in older grafts as compared with non-calcific atheromas (159±57 vs. 90±62 months after CABG, P=0.001). Heterogeneous neointima was found only in ISR (70% vs. 0, P<0.001) and was observed with similar frequency in both BMS and DES (24% vs. 30%, P=0.657). ISR was detected earlier in DES than BMS (median, 50 months; IQR, 18-96 months vs. 27 months; IQR, 13-29 months, P<0.001). CONCLUSIONS: OCT-based characteristics of de novo and ISR lesions in SVG were similar except for heterogeneous tissue, which was observed only in ISR. (Circ J 2016; 80: 1804-1811).

Stenting and Adjunctive Delivery of Paclitaxel Via Balloon Coating Versus Durable Polymeric Matrix for De Novo Coronary Lesions: Clinical and Angiographic Results from the Prospective Randomized Trial.

BACKGROUND: There is limited comparative clinical data regarding the safety and efficacy profile of paclitaxel delivery via balloon versus stent-polymer matrix. In this study, we aimed to compare the clinical and angiographic results of two different methods of paclitaxel delivery among patients undergoing percutaneous coronary intervention (PCI) for single de novo coronary lesions. METHODS: A total of 202 patients undergoing PCI due to symptomatic heart disease and at least one significant coronary artery lesion were prospectively enrolled in a multicenter non-inferiority trial. Eligible patients were randomized to a revascularization with either a paclitaxel eluting stent (PES = Coroflex Please, B.Braun) or a bare metal stent (BMS) followed by a paclitaxel coated balloon (PCB) dilation (BMS = Coroflex + PCB = Sequent Please, B.Braun). Clinical follow-up was obtained at 9 months in all patients, whereas angiographic in a subset of 94 (46.5%) patients. RESULTS: The baseline characteristics were well balanced between groups. At 9 months, the primary endpoint of in-stent late lumen loss in BMS + PCB was comparable and non-inferior to PES (0.21 ± 0.5 vs. 0.30 ± 0.7 mm, respectively. P(non-inf) < 0.05). At 9 months, the incidence of MACE (7.0 vs. 6.9%, HR = 1, 95%CI: 0.3-2.8; P = 0.99), comprising the occurrence of myocardial infarction (4.9 vs. 3.0%, HR = 1.62, 95%CI: 0.4-6.5; P = 0.32), target lesion revascularization (6.9 vs. 5.0%, HR = 1.42, 95%CI: 0.4-4.4; p = 0.54) and stent thrombosis (4.9 vs. 3.0%, HR = 2.01, 95%CI: 0.5-7.4; P = 0.74) was comparable between BMS + PCB and PES, respectively. In the BMS + PCB group, thrombosis tended to occur within 30 days (3.9 vs. 1.0%; P = 0.38). CONCLUSIONS: Paclitaxel delivery via drug coated balloon or polymer-stent matrix achieved comparable angiographic and clinical results among patients with de novo coronary lesions. BMS + PCB revascularization was associated with a higher rate of stent thrombosis when compared to newer generation drug eluting stents, therefore, should be recommended as a bail-out for PCB alone angioplasty.

FISH Amyloid - a new method for finding amyloidogenic segments in proteins based on site specific co-occurrence of aminoacids.

BACKGROUND: Amyloids are proteins capable of forming fibrils whose intramolecular contact sites assume densely packed zipper pattern. Their oligomers can underlie serious diseases, e.g. Alzheimer's and Parkinson's diseases. Recent studies show that short segments of aminoacids can be responsible for amyloidogenic properties of a protein. A few hundreds of such peptides have been experimentally found but experimental testing of all candidates is currently not feasible. Here we propose an original machine learning method for classification of aminoacid sequences, based on discovering a segment with a discriminative pattern of site-specific co-occurrences between sequence elements. The pattern is based on the positions of residues with correlated occurrence over a sliding window of a specified length. The algorithm first recognizes the most relevant training segment in each positive training instance. Then the classification is based on maximal distances between co-occurrence matrix of the relevant segments in positive training sequences and the matrix from negative training segments. The method was applied for studying sequences of aminoacids with regard to their amyloidogenic properties. RESULTS: Our method was first trained on available datasets of hexapeptides with the amyloidogenic classification, using 5 or 6-residue sliding windows. Depending on the choice of training and testing datasets, the area under ROC curve obtained the value up to 0.80 for experimental, and 0.95 for computationally generated (with 3D profile method) datasets. Importantly, the results on 5-residue segments were not significantly worse, although the classification required that algorithm first recognized the most relevant training segments. The dataset of long sequences, such as sup35 prion and a few other amyloid proteins, were applied to test the method and gave encouraging results. Our web tool FISH Amyloid was trained on all available experimental data 4-10 residues long, offers prediction of amyloidogenic segments in protein sequences. CONCLUSIONS: We proposed a new original classification method which recognizes co-occurrence patterns in sequences. The method reveals characteristic classification pattern of the data and finds the segments where its scoring is the strongest, also in long training sequences. Applied to the problem of amyloidogenic segments recognition, it showed a good potential for classification problems in bioinformatics.

Experimental evaluation of pharmacokinetic profile and biological effect of a novel paclitaxel microcrystalline balloon coating in the iliofemoral territory of swine.

BACKGROUND: New paclitaxel coated balloons (PCB) developments have been proposed to maintain therapeutic levels of drug in the tissue while decreasing particle release. In this series of studies, we evaluated the pharmacokinetic profile and biological effects after paclitaxel delivery via novel microcrystalline PCB coating (mcPCB, Pax®, Balton) in porcine iliofemoral arteries. METHODS: Ten domestic swine were enrolled yielding 24 iliofemoral segments for evaluation. In the pharmacokinetic study, nine mcPCBs were dilated for 60 sec and animals sacrificed after 1 hr, 3 and 7 days. Studied segments were harvested and tissue paclitaxel concentration was analyzed utilizing HPLC. In the biological response evaluation, self-expandable stents were implanted followed by post dilation with either mcPCB (n = 10) or POBA (n = 5). After 28 days, angiography was performed, animals were sacrificed and stented segments harvested for histopathological evaluation. RESULTS: The 1-hr, 3 and 7 days vessel paclitaxel concentrations were 152.9 ± 154.5, 36.5 ± 49.5, and 0.9 ± 0.7 ng/mg respectively. In the biological response study, stents in the mcPCB group presented lower angiographic measures of neointimal hyperplasia as expressed by late loss when compared to POBA (-0.43 ± 0.9 vs. 0.23 ± 1.2; P = 0.24) at 28 days. In the histopathological evaluation, percent area of stenosis (%AS) was reduced by 42% in the mcPCB group (P < 0.05). The healing process in mcPCB group was comparable to POBA with regard to fibrin deposition (0.7 vs. 0.7; P = ns), neointimal maturity (1.97 vs. 1.93; P = ns), inflammation score (0.92 vs. 1; P = ns) and endothelialization score (1.77 vs. 1.73; P = ns). The mcPCB group did however display a greater tendency of medial cell loss and mineralization (60% vs. 0; P = 0.08). CONCLUSIONS: Delivery of paclitaxel via a novel mcPCB resulted in low long-term tissue retention of paclitaxel. However, this technological approach displayed reduced neointimal proliferation and favorable healing profile.

Assessment of Effectiveness of the Algorithm for Automated Quantitative Analysis of Metallic Strut Tissue Short-Term Coverage with Intravascular Optical Coherence Tomography.

Background: Due to its high resolution, optical coherence tomography (OCT) is the most suitable modality for neointimal coverage assessments. Evaluation of stent healing seems crucial to accurately define their safety profile since delayed healing is connected with stent thrombosis. This study aimed to present an algorithm for automated quantitative analysis of stent strut coverage at the early stages of vessel healing in intravascular OCT. Methods: A set of 592 OCT frames from 24 patients one month following drug-eluting stent implantation was used to assess the algorithm's effectiveness. Struts not covered on any side or covered but only on one side were categorized as uncovered. The algorithm consists of several key steps: preprocessing, vessel lumen segmentation, automatic strut detection, and measurement of neointimal thickness. Results: The proposed algorithm proved its efficiency in lumen and stent area estimation versus manual reference. It showed a high positive predictive value (PPV) (89.7%) and true positive rate (TPR) (91.4%) in detecting struts. A qualitative assessment for covered and uncovered struts was characterized by high TPR (99.1% and 80%, respectively, for uncovered and covered struts) and PPV (77.3% and 87%). Conclusions: The proposed algorithm demonstrated good agreement with manual measurements. Automating the stent coverage assessment might facilitate imaging analysis, which might be beneficial in experimental and clinical settings.

Importance of Short-Term Neointimal Coverage of Drug-Eluting Stents in the Duration of Dual Antiplatelet Therapy.

Dual antiplatelet therapy (DAPT) is mandatory after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation, but optimal DAPT duration remains a topic of intense discussion. The shorter regimen of DAPT might be especially beneficial for high-bleeding-risk (HBR) patients. Novel stent platforms have been designed with innovations that should facilitate vessel healing following stent implantation and enable short DAPT. This review aimed to summarize evidence of the neointimal coverage of short-term stents and their implications for DAPT duration. Results from histological and optical coherence tomography (OCT) studies confirm the significant role of uncovered struts after the implantation of a stent in patients presenting with late stent thrombosis. Several studies have shown favorable vessel healing at one month (with 83.2% of covered struts, on average) and three months following stent implantation (with 93.3% of covered struts, on average). Solely HBR patient trials have proven that one month of DAPT can be applicable and safe in this population. Three-month DAPT was tested in a more diverse population and remains effective and safe in comparison to a longer DAPT regimen. That evidence proves that short-term DAPT might be applicable, especially for HBR patients.

Role of Lipid-Lowering and Anti-Inflammatory Therapies on Plaque Stabilization.

Atherosclerosis is the predominant underlying etiopathology of coronary artery disease. Changes in plaque phenotype from stable to high risk may spur future major adverse cardiac events (MACE). Different pharmacological therapies have been implemented to mitigate this risk. Over the last two decades, intravascular imaging modalities have emerged in clinical studies to clarify how these therapies may affect the composition and burden of coronary plaques. Lipid-lowering agents, such as statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors, were shown not only to reduce low-density lipoprotein levels and MACE but also to directly affect features of coronary plaque vulnerability. Studies have demonstrated that lipid-lowering therapy reduces the percentage of atheroma volume and number of macrophages and increases fibrous cap thickness. Future studies should answer the question of whether pharmacological plaque stabilization may be sufficient to mitigate the risk of MACE for selected groups of patients with atherosclerotic coronary disease.

Sex Differences in Fractional Flow Reserve Utilization.

Background: The literature review shows that female patients are more frequently underdiagnosed or suffer from delayed diagnosis. Recognition of sex-related differences is crucial for implementing strategies to improve cardiovascular outcomes. We aimed to assess sex-related disparities in the frequency of fractional flow reserve (FFR)-guided procedures in patients who underwent angiography and/or percutaneous coronary intervention (PCI). Methods: We have derived the data from the national registry of percutaneous coronary interventions and retrospectively analyzed the data of more than 1.4 million angiography and/or PCI procedures [1,454,121 patients (62.54% men and 37.46% women)] between 2014 and 2022. The logistic regression analysis was conducted to explore whether female sex was associated with FFR utilization. Results: The FFR was performed in 61,305 (4.22%) patients and more frequently in men than women (4.15% vs. 3.45%, p < 0.001). FFR was more frequently assessed in females with acute coronary syndrome than males (27.75% vs. 26.08%, p < 0.001); however, women with chronic coronary syndrome had FFR performed less often than men (72.25% vs. 73.92%, p < 0.001). Females with FFR-guided procedures were older than men (69.07 (±8.87) vs. 65.45 (±9.38) p < 0.001); however. less often had a history of myocardial infarction (MI) (24.79% vs. 36.73%, p < 0.001), CABG (1.62% vs. 2.55%, p < 0.005) or PCI (36.6% vs. 24.79%, p < 0.001) compared to men. Crude comparison has shown that male sex was associated with a higher frequency of FFR assessment (OR = 1.2152-1.2361, p < 0.005). Conclusions: Despite a substantial rise in FFR utilization, adoption in women remains lower than in men. Female sex was found to be an independent negative predictor of FFR use.

Drug-Eluting Stents: Technical and Clinical Progress.

Drug-eluting stents (DES) demonstrated superior efficacy when compared to bare metal stents and plain-old balloon angioplasty and are nowadays used in almost all percutaneous revascularization procedures. The design of the stent platforms is constantly improving to maximize its efficacy and safety. Constant development of DES includes adoption of new materials used for scaffold production, new design types, improved overexpansion abilities, new polymers coating and, finally, improved antiproliferative agents. Especially nowadays, with the immense number of available DES platforms, it is crucial to understand how different aspects of stents impact the effect of their implantation, as subtle differences between various stent platforms could impact the most important issue-clinical outcomes. This review discusses the current status of coronary stents and the impact of stent material, strut design and coating techniques on cardiovascular outcomes.

Robotic-Assisted Solutions for Invasive Cardiology, Cardiac Surgery and Routine On-Ward Tasks: A Narrative Review.

Robots are defined as programmable machines that can perform specified tasks. Medical robots are emerging solutions in the field of cardiology leveraging recent technological innovations of control systems, sensors, actuators, and imaging modalities. Robotic platforms are successfully applied for percutaneous coronary intervention, invasive cardiac electrophysiology procedures as well as surgical operations including minimally invasive aortic and mitral valve repair, coronary artery bypass procedures, and structural heart diseases. Furthermore, machines are used as staff-assisting tools to support nurses with repetitive clinical duties i.e., food delivery. High precision and resolution allow for excellent maneuverability, enabling the performance of medical procedures in challenging anatomies that are difficult or impossible using conventional approaches. Moreover, robot-assisted techniques protect operators from occupational hazards, reducing exposure to ionizing radiation, and limiting risk of orthopedic injuries. Novel automatic systems provide advantages for patients, ensuring device stability with optimized utilization of fluoroscopy. The acceptance of robotic technology among healthcare providers as well as patients paves the way for widespread clinical application in the field of cardiovascular medicine. However, incorporation of robotic systems is associated with some disadvantages including high costs of installation and expensive disposable instrumentations, the need for large operating room space, and the necessity of dedicated training for operators due to the challenging learning curve of robotic-assisted interventional systems.

Impact of smoking on outcomes in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

INTRODUCTION: Smoking is a well­established risk factor for cardiovascular diseases. However, in patients with ST­segment elevation myocardial infarction (STEMI), smoking has been associated with better clinical outcomes; this phenomenon became known as the "smoker's paradox." OBJECTIVES: The aim of this study was to evaluate the association between smoking and clinical outcomes in STEMI patients treated with primary percutaneous coronary intervention (PCI), using 3 large national registries. PATIENTS AND METHODS: We retrospectively analyzed the data of 82 235 hospitalized STEMI patients treated with primary PCI. Among the analyzed population, 30 966 patients (37.96%) were smokers, and 51 269 (62.36%) were nonsmokers. We evaluated the baseline characteristics, pharmacotherapy, clinical outcomes, and readmission causes in a 36­month follow­up. RESULTS: The smokers were significantly younger (median [interquartile range] age, 58 [52-64] vs 68 [59-77] years; P <0.001) than the nonsmokers, and there were more men in this group. The patients who smoked were less likely to have traditional risk factors, as compared with the nonsmokers. In the unadjusted analysis, in­hospital and 36­month mortality and rehospitalization rates were lower in the smokers group. However, after adjustment for baseline characteristics that differed between the 2 groups, the multivariable analysis showed that tobacco use was one of the independent risk factors for 36­month mortality (hazard ratio, 1.11; 95% CI, 1.06-1.18; P <0.001). CONCLUSIONS: In the present large­scale, registry­based analysis, the observed lower 36­month crude rates of adverse events among the smokers, as compared with the nonsmokers, might be partially explained by a significantly lower burden of traditional risk factors and younger age of the smokers. After accounting for age and other baseline differences, smoking was found to be one of the independent risk factors for 36­month mortality.

Long-term outcomes of patients with normal fractional flow reserve and thin-cap fibroatheroma.

BACKGROUND: The long-term prognostic implications of fractional flow reserve (FFR)-negative lesions hosting vulnerable plaques remain unsettled. AIMS: The aim of this study was to evaluate the association of non-ischaemic lesions hosting optical coherence tomography (OCT)-detected thin-cap fibroatheromas (TCFA) with first and recurrent cardiovascular events during follow-up up to 5 years in a diabetes mellitus (DM) patient population. METHODS: COMBINE OCT-FFR is a prospective, international, double-blind, natural history study. Patients with DM and with ≥1 FFR-negative lesion were classified into 2 groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint (PE) is a composite of cardiac mortality, target vessel-related myocardial infarction (TV-MI), clinically driven target lesion revascularisation (TLR), or unstable angina (UA) requiring hospitalisation during follow-up up to 5 years. RESULTS: Among 390 DM patients (age 67.5±9 years; 37% female) with ≥1 FFR-negative lesion, 292 (74.9%) were TCFA-negative while 98 (25.1%) were TCFA-positive. The PE occurred more frequently in TCFA-positive than in TCFA-negative patients (21.4% vs 8.2%, hazard ratio [HR] 2.89, 95% confidence interval [CI]: 1.61-5.20; p<0.001; 6.42 vs 2.46 events per 100 patient-years, rate ratio [RR] 2.61, 95% CI: 1.38-4.90; p=0.002). Furthermore, when TV-MI, TLR, and UA were treated as recurrent components of the PE, TCFA-positive patients experienced a higher risk of recurrent events (HR 2.89, 95% CI; 1.74-4.80; p<0.001; 13.45 vs 2.87 events per 100 patient-years, RR 4.69, 95% CI: 2.86-7.83; p<0.001). A multivariable analysis identified the presence of TCFA as an independent predictor of the PE (HR 2.76, 95% CI: 1.53-4.97; p<0.001). CONCLUSIONS: OCT-detected TCFA-positive lesions, although not ischaemia-generating, are associated with an increased risk of adverse events during long-term follow-up. CLINICALTRIALS: gov: NCT02989740.

Morphological characteristics of lesions with thin cap fibroatheroma-a substudy from the COMBINE (OCT-FFR) trial.

AIMS: To study if any qualitative or quantitative optical coherence tomography (OCT) variables in combination with thin cap fibroatheroma (TCFA) patients could improve the identification of lesions at risk for future major adverse cardiac events (MACEs). METHODS AND RESULTS: From the combined optical coherence tomography morphologic and fractional flow reserve hemodynamic assessment of non- culprit lesions to better predict adverse event outcomes in diabetes mellitus patients: COMBINE (OCT-FFR) trial database (NCT02989740), we performed a detailed assessment OCT qualitative and quantitative variables in TCFA carrying diabetes mellitus (DM) patients with vs. without MACE during follow-up. MACEs were defined as a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, and hospitalization for unstable angina. From the 390 fractional flow reserve (FFR)-negative DM patients, 98 (25.2%) had ≥1 OCT-detected TCFA, of which 13 (13.3%) had MACE and 85 (86.7%) were event-free (non-MACE). The baseline characteristics were similar between both groups; however, a smaller minimal lumen area (MLA) and lower mean FFR value were observed in MACE group (1.80 vs. 2.50 mm2, P = 0.01, and 0.85 vs. 0.89, P = 0.02, respectively). Prevalence of healed plaque (HP) was higher in the MACE group (53.85 vs. 21.18%, P = 0.01). TCFA were predominantly located proximal to the MLA. TCFA area was smaller in the MACE group, while no difference was observed regarding the lesion area. CONCLUSION: Within TCFA carrying patients, a smaller MLA, lower FFR values, and TCFA location adjacent to a HP were associated with future MACE. Carpet-like measured lesion area surface was similar, while the TCFA area was smaller in the MACE arm, and predominantly located proximal to the MLA.

'Ref! Could You Help Me?'-Building a Positive Climate by Referees during Floorball Competitions in Youth Sport.

In creating a positive climate in sport for children and youth, the role of adults is of key importance as their behavior and attitudes determine the experiences and multilateral development of young players. Relatively recently, the importance of the referee in creating a supportive sporting environment has begun to be emphasized. This concerns, in particular, team sports in which the referees interact with players many times and influence the course of the game. The aim of the study was to evaluate the quality of the referee-players' interactions during youth floorball matches in terms of building a positive climate and responsiveness to the players' needs. Another aim of the study was to examine whether the referee's qualifications and players' gender affect the quality of their interactions with the players. The study was conducted among 21 referees officiating matches for girls and boys aged 12-18. Naturalistic and structured observation methods were used in the study. The observation was conducted using a wireless intercom that allows listening to verbal messages directed to the players. Furthermore, the referee's work was recorded using a camera. The results of the statistical tests did not show any significant differences in the assessment of referees between the groups distinguished in terms of the referees' license and players' gender in both examined dimensions. The observations showed that the average rating of building a positive climate by referees during a sporting event measured on a seven-point scale was 'poor' (2.81 pts). The referees were assessed significantly higher on the second dimension (responsiveness to the players' needs), although an overall rating of 3.81 pts means a medium level of interaction quality. The results indicate areas in which referees can improve. They lead to the following conclusions: (i) the contents of training for floorball referees should include problems of pedagogy and developmental psychology; (ii) referees should be equipped with appropriate competencies for building a positive climate during matches and monitoring the players' needs; (iii) referees appointed to officiate children and youth games should be characterized by appropriate predispositions.