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Abstract: 5-Alkylidene-2,5-dihydroisoxazoles and 5-alkylidenamine-2,5-dihydroisoxazoles were easily prepared from the corresponding 5-chloro-2-methylisoxazolium triflate and an enolizable compound or alkylamine. Their photochemical reactivity leads to photoisomers that in some cases constitute new heterocycles systems. The photorearrangement involves either triplet or singlet state depending on substituents and experimental conditions. [Copyright &y& Elsevier]

Background: Coronary access after transcatheter aortic valve implantation (TAVI) with supra-annular self-expandable valves may be challenging or un-feasible. There is little data concerning coronary access following transcatheter aortic valve-in-valve implantation (ViV-TAVI) for degenerated surgical bioprosthesis., Aims: To evaluate the feasibility and challenge of coronary access after ViV-TAVI with the supra-annular self-expandable ACURATE neo valve., Materials and Methods: Sixteen patients underwent ViV-TAVI with the ACURATE neo valve. Post-procedural computed tomography (CT) was used to create 3D-printed life-sized patient-specific models for bench-testing of coronary cannulation. Primary endpoint was feasibility of diagnostic angiography and PCI. Secondary endpoints included incidence of challenging cannulation for both diagnostic catheters (DC) and guiding catheters (GC). The association between challenging cannulations with aortic and transcatheter/surgical valve geometry was evaluated using pre and post-procedural CT scans., Results: Diagnostic angiography and PCI were feasible for 97 and 95% of models respectively. All non-feasible procedures occurred in ostia that underwent prophylactic "chimney" stenting. DC cannulation was challenging in 17% of models and was associated with a narrower SoV width (30 vs. 35 mm, p < 0.01), STJ width (28 vs. 32 mm, p < 0.05) and shorter STJ height (15 vs. 17 mm, p < 0.05). GC cannulation was challenging in 23% of models and was associated with narrower STJ width (28 vs. 32 mm, p < 0.05), smaller transcatheter-to-coronary distance (5 vs. 9.2 mm, p < 0.05) and a worse coronary-commissural overlap angle (14.3° vs. 25.6 o , p < 0.01). Advanced techniques to achieve GC cannulation were required in 22/64 (34%) of cases., Conclusion: In this exploratory bench analysis, diagnostic angiography and PCI was feasible in almost all cases following ViV-TAVI with the ACURATE neo valve. Prophylactic coronary stenting, higher implantation, narrower aortic sinus dimensions and commissural misalignment were associated with an increased challenge of coronary cannulation., Competing Interests: AK has received speaker fees from Boston Scientific. AM received an institutional grant from Boston Scientific. W-KK has received personal fees from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, and Meril Sciences. DD was scientific advisor to Boston Scientific. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Khokhar, Ponticelli, Zlahoda-Huzior, Chandra, Ruggiero, Toselli, Gallo, Cereda, Sticchi, Laricchia, Regazzoli, Mangieri, Reimers, Biscaglia, Tumscitz, Campo, Mikhail, Kim, Colombo, Dudek and Giannini.)

Refractory angina represents the final stage of chronic coronary artery disease, where anginal symptoms persist despite complete epicardial coronary artery revascularization and maximally tolerated pharmacological therapy. Percutaneous narrowing of the coronary sinus with the coronary sinus reducer (Reducer ® , Neovasc, Inc., Richmond, Canada) device was first attempted in humans in 2005 and has been shown to improve angina symptoms and the quality of life of patients suffering chronic refractory angina. It was recently included in the European guidelines for the management of chronic coronary syndrome and is progressively gaining popularity. The authors hereby provide a review of current literature on the topic, intending to facilitate insights and to promote further research on this device and its clinical applications.

Background: Clinical efficacy of coronary sinus reducer (CSR) in refractory angina (RA) patients with ischemia due to the chronic total occlusion (CTO) of the right coronary artery (RCA) remains unknown., Aims: To evaluate the efficacy of CSR implantation in RA patients with CTO RCA and compare them to CSR recipients with left coronary artery (LCA) ischemia., Methods: Consecutive patients with CTO RCA from 2 centers were prospectively included and compared to patients with LCA ischemia. All patients underwent evaluation of angina severity and quality of life (QoL) at baseline and after 12 months. In a subgroup of CTO RCA patients, stress cardiac magnetic resonance (CMR) imaging was also performed., Results: Twenty-two patients with CTO RCA and predominant inferior and/or inferoseptal wall ischemia (the CTO RCA group) were compared to 24 patients with predominant anterior, lateral, and/or anteroseptal wall ischemia (the LCA group). While the Canadian Cardiovascular Society (CCS) anginascore mean (SD) improved in the CTO RCA group from 2.73 (0.46) to 1.82 (0.73) (P <0.001) and in the LCA group from 2.67 (0.57) to 1.92 (0.72) (P <0.001), there was no intergroup difference (P = 0.350). Significant improvement in all domains of the Seattle Angina Questionnaire was observed. Stress CMR did not show a significant reduction of ischemic inferior and/or inferoseptal segments, however, improvements in the transmurality index (P = 0.03) and the myocardial perfusion reserve index in segments with inducible ischemia (P = 0.03) were observed in the CTO RCA group., Conclusions: In CTO RCA patients, CSR implantation alleviated angina symptoms and improved QoL. The extent of improvement was comparable to that observed in patients with LCA ischemia.

Background: Refractory angina affects an increasing proportion of the population with advanced coronary artery disease and microvascular dysfunction. Limited effective pharmacological and interventional therapies exist for this patient cohort. The coronary sinus (CS) reducer, recently recommended in the 2019 guidelines of the European Society of Cardiology for the management of chronic refractory angina, is a balloon-expandable, stainless-steel device designed for implantation in the CS. It acts by increasing CS pressure, thereby redistributing blood to ischemic myocardium, relieving symptoms, and improving quality of life. However, between 15%-30% of patients do not respond to this treatment. Six mechanisms appear to explain this poor response to CS reducer therapy: (1) inappropriate patient selection; (2) cardiac venous system heterogeneity; (3) CS size; (4) incomplete device endothelialization; (5) coronary artery disease phenotype and progression; and (6) limited myocardial ischemia at baseline. We hereby review these mechanisms in detail and highlight key areas that should be addressed in order to try and reduce the burden of non-responders following CS reducer implantation.

Background: Valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) is an emerging alternative to re-do surgery. However, the challenge of coronary access (CA) following ViV-TAVR is a potential limitation as TAVR expands to younger lower-risk populations., Objectives: Using post-implantation computed tomography (CT) scans to evaluate the geometrical relationship between coronary ostia and valve frame in patients undergoing ViV-TAVR with the ACURATE neo valve., Methods: Post-implant CT scans of 18 out of 20 consecutive patients treated with the ACURATE neo valve were analyzed. Coronary ostia location in relation to the highest plane (HP) (highest point of the ACURATE neo or surgical valve) was determined. Ostia located below the highest plan were further subclassified according to the gap available between the transcatheter heart valve frame and ostium (transcatheter-to-coronary [TTC] distance). The impact implantation depth has on these geometrical relationships was evaluated., Results: A total of 21 out of 36 coronary ostia (58%) were located below the level of the HP with the left coronary artery (36%) more likely to be affected than the right (22%). Further sub-classification of these ostia revealed a large (>6 mm), moderate (4-6 mm), and small (<4 mm) TTC distance in 57% (12/21), 38% (8/21), and in 6% (1/18) of cases, respectively. At an implantation depth <4 mm compared to >4 mm, all ostia were located below the HP with no difference in post-procedural mean gradients (14.5 mmHg ± 4.7 vs. 12.6 mmHg ± 5.8; p = .5, 95%CI 3.8-7.5)., Conclusions: CA following ACURATE neo implantation for ViV-TAVR could potentially be challenging in a significant proportion of patients and specific consideration should be given to the implantation depth., (© 2021 Wiley Periodicals LLC.)

Background: Coronavirus disease 2019 (COVID-19) has spread worldwide determining dramatic impacts on healthcare systems. Early identification of high-risk parameters is required in order to provide the best therapeutic approach. Coronary, thoracic aorta and aortic valve calcium can be measured from a non-gated chest computer tomography (CT) and are validated predictors of cardiovascular events and all-cause mortality. However, their prognostic role in acute systemic inflammatory diseases, such as COVID-19, has not been investigated., Objectives: The aim was to evaluate the association of coronary artery calcium and total thoracic calcium on in-hospital mortality in COVID-19 patients., Methods: 1093 consecutive patients from 16 Italian hospitals with a positive swab for COVID-19 and an admission chest CT for pneumonia severity assessment were included. At CT, coronary, aortic valve and thoracic aorta calcium were qualitatively and quantitatively evaluated separately and combined together (total thoracic calcium) by a central Core-lab blinded to patients' outcomes., Results: Non-survivors compared to survivors had higher coronary artery [Agatston (467.76 ​± ​570.92 vs 206.80 ​± ​424.13 ​mm 2 , p ​< ​0.001); Volume (487.79 ​± ​565.34 vs 207.77 ​± ​406.81, p ​< ​0.001)], aortic valve [Volume (322.45 ​± ​390.90 vs 98.27 ​± ​250.74 mm 2 , p ​< ​0.001; Agatston 337.38 ​± ​414.97 vs 111.70 ​± ​282.15, p ​< ​0.001)] and thoracic aorta [Volume (3786.71 ​± ​4225.57 vs 1487.63 ​± ​2973.19 mm 2 , p ​< ​0.001); Agatston (4688.82 ​± ​5363.72 vs 1834.90 ​± ​3761.25, p ​< ​0.001)] calcium values. Coronary artery calcium (HR 1.308; 95% CI, 1.046-1.637, p ​= ​0.019) and total thoracic calcium (HR 1.975; 95% CI, 1.200-3.251, p ​= ​0.007) resulted to be independent predictors of in-hospital mortality., Conclusion: Coronary, aortic valve and thoracic aortic calcium assessment on admission non-gated CT permits to stratify the COVID-19 patients in-hospital mortality risk., (Copyright © 2021 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Aim: Coronary sinus (CS) reducer implantation is associated with symptomatic relief of patients with refractory angina. However, 15% to 30% of the patients do not respond to this treatment. Aim if this study was to evaluate the effect of CS size in the effectiveness of the device., Methods: Prior to device implantation and at 4-month resting ventricular function was assessed by stress cardiac magnetic resonance. Ischemia was assessed by the myocardial perfusion reserve index (MPRI)., Results: Fifteen patients (66 ± 10 years) underwent successful CS Reducer implantation, with improvements in angina class and exercise tolerance. Patients with a smaller CS size (<5.8 mm) presented a significantly higher percentage increase in MPRI (63 ± 51 vs 9 ± 30%, P = .03) and a higher reduction in left ventricle end-diastolic volumes., Conclusions: Greater benefits, in terms of ischemia improvement, after CS Reducer implantation were seen in patients with smaller CS sizes, suggesting a potential mechanism underlying the observed rates of reducer non-responsiveness., (© 2021 Wiley Periodicals LLC.)