TransCatheter aortic valve implantation and fractional flow reserve-guided percutaneous coronary intervention versus conventional surgical aortic valve replacement and coronary bypass grafting for treatment of patients with aortic valve stenosis and multivessel or advanced coronary disease: The transcatheter valve and vessels trial (TCW trial): Design and rationale.

BACKGROUND: Patients with severe aortic stenosis (AS) frequently present with concomitant obstructive coronary artery disease (CAD). In those, current guidelines recommend combined coronary artery bypass grafting (CABG) and surgical aortic valve replacement (SAVR) as the preferred treatment option, although this surgical approach is associated with a high rate of clinical events. Combined transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI) with or without FFR have evolved as a valid alternative for cardiac surgery in patients with AS and multivessel or advanced CAD. To date, no dedicated trial has prospectively evaluated the outcomes of a percutaneous versus surgical treatment for patients with both severe AS and CAD. AIMS: To investigate whether fractional-flow reserve (FFR)-guided PCI and TAVI is noninferior to combined CABG and SAVR for the treatment of severe AS and multivessel or advanced CAD. METHODS: The Transcatheter Valve and Vessels (TCW) trial (clinicaltrial.gov: NCT03424941) is a prospective, randomized, controlled, open label, international trial. Patients ≥ 70 years with severe AS and multivessel (≥ 2 vessels) or advanced CAD, deemed feasible by the heart team for both; a full percutaneous or surgical treatment, will be randomised in a 1:1 fashion to either FFR-guided PCI followed by TAVI (intervention arm) vs. CABG and SAVR (control arm). The primary endpoint is a patient-oriented composite of all-cause mortality, myocardial infarction, disabling stroke, unscheduled clinically-driven target vessel revascularization, valve reintervention, and life threatening or disabling bleeding at 1 year. The TCW trial is powered for noninferiority, and if met, superiority will be tested. Assuming a primary endpoint rate of 30% in the CABG-SAVR arm, with a significance level α of 5%, a noninferiority limit delta of 15% and a loss to follow-up of 2%, a total of 328 patients are needed to obtain a power of 90%. The primary endpoint analysis is performed on an intention-to-treat basis. SUMMARY: The TCW Trial is the first prospective randomized trial that will study if a less invasive percutaneous treatment for severe AS and concomitant advanced CAD (i.e., FFR-guided PCI-TAVI) is noninferior to the guidelines recommended approach (CABG-SAVR).

Safety and Healthcare Resource Utilization in Patients Undergoing Left Atrial Appendage Closure-A Nationwide Analysis.

Percutaneous left atrial appendage closure (LAAC) has emerged as a non-pharmacological alternative for stroke prevention in patients with atrial fibrillation (AF) not suitable for anticoagulation therapy. Real-world data on peri-procedural outcomes are limited. The aim of this study was to analyze outcomes of peri-procedural safety and healthcare resource utilization in 11,240 adult patients undergoing LAAC in the United States between 2016 and 2019. Primary outcomes (safety) were in-hospital ischemic stroke or systemic embolism (SE), pericardial effusion (PE), major bleeding, device embolization and mortality. Secondary outcomes (resource utilization) were adverse discharge disposition, hospital length of stay (LOS) and costs. Logistic and Poisson regression models were used to analyze outcomes by adjusting for 10 confounders. SE decreased by 97% between 2016 and 2019 [95% Confidence Interval (CI) 0-0.24] (p = 0.003), while a trend to lower numbers of other peri-procedural complications was determined. In-hospital mortality (0.14%) remained stable. Hospital LOS decreased by 17% (0.78-0.87, p < 0.001) and adverse discharge rate by 41% (95% CI 0.41-0.86, p = 0.005) between 2016 and 2019, while hospital costs did not significantly change (p = 0.2). Female patients had a higher risk of PE (OR 2.86 [95% CI 2.41-6.39]) and SE (OR 5.0 [95% CI 1.28-43.6]) while multi-morbid patients had higher risks of major bleeding (p < 0.001) and mortality (p = 0.031), longer hospital LOS (p < 0.001) and increased treatment costs (p = 0.073). Significant differences in all outcomes were observed between male and female patients across US regions. In conclusion, LAAC has become a safer and more efficient procedure. Significant sex differences existed across US regions. Careful considerations should be taken when performing LAAC in female and comorbid patients.

Transcatheter Caval Valve Implantation for Tricuspid Regurgitation After Single Leaflet Device Attachment.

An 86-year-old patient experienced progressive heart failure symptoms. Echocardiographic evaluation revealed severe tricuspid regurgitation, which was treated by transcatheter edge-to-edge repair. During the procedure, single leaflet device attachment occurred. On the basis of a prohibitive surgical risk, caval valve implantation was performed, with no notable complications. (Level of Difficulty: Advanced.).

Disease Severity in Moderate-to-Severe COVID-19 Is Associated With Platelet Hyperreactivity and Innate Immune Activation.

Background: Hemostasis and inflammation are both dysregulated in patients with moderate-to-severe coronavirus disease 2019 (COVID-19). Yet, both processes can also be disturbed in patients with other respiratory diseases, and the interactions between coagulation, inflammation, and disease severity specific to COVID-19 are still vague. Methods: Hospitalized patients with acute respiratory symptoms and with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-positive (COVpos) and SARS-CoV2-negative (COVneg) status were included. We assessed adenosine diphosphate (ADP)-, thrombin receptor activator peptide 6 (TRAP)-, and arachidonic acid (AA)-induced platelet reactivity by impedance aggregometry, as well as leukocyte subtype spectrum and platelet-leukocyte aggregates by flow cytometry and inflammatory cytokines by cytometric bead array. Results: ADP-, TRAP-, and AA-induced platelet reactivity was significantly higher in COVpos than in COVneg patients. Disease severity, assessed by sequential organ failure assessment (SOFA) score, was higher in COVpos than in COVneg patients and again higher in deceased COVpos patients than in surviving COVpos. The SOFA score correlated significantly with the mean platelet volume and TRAP-induced platelet aggregability. A larger percentage of classical and intermediate monocytes, and of CD4pos T cells (TH) aggregated with platelets in COVpos than in COVneg patients. Interleukin (IL)-1 receptor antagonist (RA) and IL-6 levels were higher in COVpos than in COVneg patients and again higher in deceased COVpos patients than in surviving COVpos. IL-1RA and IL-6 levels correlated with the SOFA score in COVpos but not in COVneg patients. In both respiratory disease groups, absolute levels of B-cell-platelet aggregates and NK-cell-platelet aggregates were correlated with ex vivo platelet aggegation upon stimulation with AA and ADP, respectively, indicating a universal, but not a COVID-19-specific mechanism. Conclusion: In moderate-to-severe COVID-19, but not in other respiratory diseases, disease severity was associated with platelet hyperreactivity and a typical inflammatory signature. In addition to a severe inflammatory response, platelet hyperreactivity associated to a worse clinical outcome in patients with COVID-19, pointing to the importance of antithrombotic therapy for reducing disease severity.

Clinical outcomes by optical characteristics of neointima and treatment modality in patients with coronary in-stent restenosis.

BACKGROUND: Drug-coated balloons (DCB) and drug-eluting stents (DES) represent the currently recommended treatments for in-stent restenosis (ISR). Optical coherence tomography (OCT) allows detailed neointimal characterisation which can guide treatment strategies. AIMS: The aims of this study were first, to assess the relation between neointimal pattern and clinical outcomes following in-stent restenosis (ISR) treatment, and second, to explore a potential interaction between neointimal pattern and treatment modality relative to clinical outcomes. METHODS: Patients undergoing OCT-guided treatment (DCB or DES) of ISR in three European centres were included. Based on the median of distribution of non-homogeneous neointima quadrants, patients were categorised into low and high inhomogeneity groups. RESULTS: A total of 197 patients (low inhomogeneity=100 and high inhomogeneity=97) were included. There were no significant differences in terms of major adverse cardiac events (MACE) (p=0.939) or target lesion revascularisation (TLR) (p=0.732) between the two groups. The exploratory analysis showed a significant interaction between neointimal pattern and treatment modality regarding MACE (pint=0.006) and TLR (pint=0.022). DES showed a significant advantage over DCB in the high (MACE: HR 0.26 [0.10-0.65], p=0.004; TLR: HR 0.28 [0.11-0.69], p=0.006), but not in the low inhomogeneity group (MACE: p=0.917; TLR: p=0.797). CONCLUSIONS: In patients with ISR treated with DCB or DES, there were no significant differences in terms of MACE or TLR between the low and high inhomogeneity groups. A significant interaction was observed between treatment modality and neointimal pattern with an advantage of DES over DCB in the high and no difference in the low inhomogeneity group. This warrants confirmation from prospective dedicated studies.

Intracardiac echocardiography to enable successful edge-to-edge transcatheter tricuspid valve repair in patients with insufficient TEE quality.

BACKGROUND: Transesophageal echocardiography (TEE) as a guiding tool for edge-to-edge transcatheter tricuspid valve repair (EETVr) using MitraClip (Abbott Vascular, Santa Clara, USA) may not offer sufficient image quality in a significant proportion of patients. OBJECTIVES: Intracardiac echocardiography (ICE) as additional guiding tool in EETVr with the MitraClip device. METHODS: Appropriate angulations of the ICE catheter to visualize each commissure of the tricuspid valve were established in 3D printed heart models. In a single tertiary-care center ICE was used to support EETVr as additional guidance when TEE image quality was insufficient. Procedural safety and outcomes up to 30-days were compared between ICE/TEE and TEE only guided patients. RESULTS: In 6 of 11 patients (54.5%) undergoing EETVr with MitraClip TEE alone was unsatisfactory, necessitating additional ICE guidance. In 4 of these 6 patients ICE enabled a successful completion of the procedure. The steering maneuvers identified in the 3D models were well applicable in all patients, providing examples for potential future ICE implementation in EETVr. Under both TEE alone (n = 5) and ICE (n = 6) guidance the rate of procedural complications was 0%. According to vena contracta values at discharge significant TR reduction was achievable in the treated cohort (p = 0.011). At 30-days follow-up one patient (ICE guided) died following global heart failure, not associated with the procedure itself. CONCLUSIONS: ICE guidance may offer an additional tool to guide EETVr with the MitraClip device in patients with poor TEE quality, as it enables successful results without impairing procedural safety.

Subintimal Versus Intraplaque Recanalization of Coronary Chronic Total Occlusions: Mid-Term Angiographic and OCT Findings From the ISAR-OCT-CTO Registry.

OBJECTIVES: The aim of this study was to compare angiographic and optical coherence tomography findings following subintimal as opposed to intraplaque recanalization of chronic total occlusions (CTOs). BACKGROUND: There is ongoing controversy regarding outcomes of intraplaque versus subintimal CTO recanalization. METHODS: Consecutive patients undergoing angiography and intravascular optical coherence tomography following CTO recanalization were included in the ISAR-OCT-CTO (Intracoronary Stenting and Angiographic Results - Optical Coherence Tomography for Chronic Total Occlusions) registry. The study endpoints were percent diameter stenosis and late lumen loss as well as rate of uncovered and malapposed struts. Independent correlates of uncovered and malapposed struts were assessed by multivariate analysis. RESULTS: The study included 75 patients. Intraplaque and dissection and re-entry techniques (DART) were used in 46 and 29 patients, respectively. There were no differences in terms of in-segment percent diameter stenosis (median 36.9 [interquartile range (IQR): 26.4 to 43.1] vs. 31.2 [IQR: 23.2 to 49.5]; p = 0.656), in-stent late lumen loss (0.215 mm [IQR: 0.063 to 0.495 mm] vs. 0.230 mm [IQR: 0.060 to 0.645 mm]; p = 0.837), or in-segment late lumen loss (0.030 mm [IQR: -0.278 to 0.510 mm] vs. 0.130 mm [IQR: -0.120 to 0.500 mm]; p = 0.395) at follow-up between the 2 techniques. Optical coherence tomography analysis showed comparable strut coverage (79.9% vs. 71.3%; p = 0.255) but significantly higher strut malapposition (6.6% vs. 13.6%; p < 0.001) following DART. Use of DART independently correlated with presence of strut malapposition (odds ratio: 3.41; 95% confidence interval: 1.24 to 9.36; p = 0.017) but not of strut coverage (odds ratio: 0.65; 95% confidence interval: 0.28 to 1.49; p = 0.314). CONCLUSIONS: Intraplaque and subintimal recanalization techniques are associated with comparable mid-term angiographic results. Although the rate of uncovered struts is high following CTO recanalization, the recanalization technique does not independently correlate with presence of uncovered struts. There is a high rate of strut malapposition following CTO recanalization, particularly if achieved by means of DART.

Qualitative and quantitative neointimal characterization by optical coherence tomography in patients presenting with in-stent restenosis.

AIMS: To describe optical coherence tomography (OCT) findings in patients with in-stent restenosis (ISR) and determine predictors of neointimal patterns and neoatherosclerosis. METHODS AND RESULTS: Patients undergoing OCT prior to PCI for ISR in three European centres were included. Analyses were performed in a core laboratory. Qualitative and quantitative [gray-scale signal intensity (GSI)] neointima analyses were performed on a per quadrant basis. A total of 107 patients were included. Predominantly homogeneous lesions included 4.5% (0.0-14.3) non-homogeneous quadrants, while predominantly non-homogeneous ones included 28.1% (20.3-37.5) homogeneous quadrants. Mean GSI values differed significantly between homogeneous [108.4 (92.5-123.6)], non-homogeneous [79.9 (61.2-95.9)], and neoatherosclerosis [88.3 (72.8-104.9)] quadrants (p < 0.001 for all comparisons). Stent underexpansion was observed in 48.5% and 61.1% of lesions, respectively (p = 0.225). Female sex and maximal neointimal thickness independently correlate with a non-homogeneous pattern, while angiographic pattern and diabetes mellitus inversely correlate with such pattern. Time from index stenting procedure was the only independent predictor of neoatherosclerosis. CONCLUSIONS: Different neointimal patterns coexist in a significant proportion of ISR lesions. GSI values differ significantly between neointimal categories. Neoatherosclerosis is a time-dependent phenomenon, displaying different time courses in DES compared to BMS, with earlier appearance in the former group. Stent underexpansion is a frequent finding in patients with ISR.