Distal Versus Conventional Radial Access for Coronary Angiography and Intervention The DISCO RADIAL Trial

BACKGROUND Currently, transradial access (TRA) is the recommended access for coronary procedures because of increased safety, with radial artery occlusion (RAO) being its most frequent complication, which will increasingly affect patients undergoing multiple procedures during their lifetimes. Recently, distal radial access (DRA) has emerged as a promising alternative access to minimize RAO risk. A large-scale, international, randomized trial comparing RAO with TRA and DRA is lacking. OBJECTIVES The aim of this study was to assess the superiority of DRA compared with conventional TRA with respect to forearm RAO. METHODS DISCO RADIAL (Distal vs Conventional Radial Access) was an international, multicenter, randomized controlled trial in which patients with indications for percutaneous coronary procedure using a 6-F Slender sheath were randomized to DRA or TRA with systematic implementation of best practices to reduce RAO. The primary endpoint was the incidence of forearm RAO assessed by vascular ultrasound at discharge. Secondary endpoints include crossover, hemostasis time, and access site-related complications. RESULTS Overall, 657 patients underwent TRA, and 650 patients underwent DRA. Forearm RAO did not differ between groups (0.91% vs 0.31%; P = 0.29). Patent hemostasis was achieved in 94.4% of TRA patients. Crossover rates were higher with DRA (3.5% vs 7.4%; P = 0.002), and median hemostasis time was shorter (180 vs 153 minutes; P < 0.001). Radial artery spasm occurred more with DRA (2.7% vs 5.4%; P = 0.015). Overall bleeding events and vascular complications did not differ between groups. CONCLUSIONS With the implementation of a rigorous hemostasis protocol, DRA and TRA have equally low RAO rates. DRA is associated with a higher crossover rate but a shorter hemostasis time. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Značenje vremena od dolaska u prvu zdravstvenu ustanovu do postizanja reperfuzije i ukupnog trajanja ishemije u bolesnika s akutnim infarktom miokarda s ST-elevacijom liječenih primarnom perkutanom koronarnom intervencijom

The aim of the study was to evaluate the influence of door-to-balloon time and symptom onset-to-balloon time on the prognosis of patients with acute ST-elevation myocardial infarction (STEMI ) treated with primary percutaneous coronary intervention (PCI) in the Croatian Primary PCI Network. A total of 1190 acute STEMI patients treated with primary PCI were prospectively investigated in eight centers across Croatia (677 non-transferred, 513 transferred). All patients were divided according to door-to-balloon time in three subgroups (180 minutes) and according to symptom onset-to-balloon time in three subgroups (360 minutes). The postprocedural Thrombolysis in Myocardial Infarction flow, in-hospital mortality, and major adverse cardiovascular events (mortality, pectoral angina, restenosis, reinfarction, coronary artery by-pass graft and cerebrovascular accident rate) in six-month follow-up were compared between the subgroups. The Croatian Primary PCI Network ensures results of treatment of acute STEMI comparable with randomized studies and registries abroad. None of the result differences among the door-to-balloon time subgroups was statistically significant. Considering the symptom onset-to-balloon time subgroups, a statistically significant difference at multivariate level was highest for in-hospital mortality in the subgroup of patients with longest onset-to-balloon time (4.5 vs.2.6 vs. 5.7%; p=0.04). Door-to-balloon time is one of the metrics of organization quality of primary PCI network and targets for quality improvement, but without an impact on early and sixmonth follow-up results of treatment for acute STEMI . Symptom onset-to-balloon time is more accurate for this purpose; unfortunately, reduction of the symptom onset-to-balloon time is more complex than reduction of the former.Cilj studije bio je procijeniti utjecaj vremena od dolaska u prvu zdravstvenu ustanovu do postizanja reperfuzije (engl. door-to-balloon time) i vremena od početka simptoma do postizanja reperfuzije (engl. symptom onset-to-balloon time) na prognozu bolesnika s akutnim infarktom miokarda s ST-elevacijom (STEMI ) liječenih primarnom perkutanom koronarnom intervencijom (PCI) u sklopu Hrvatske mreže primarne PCI. Autori su prospektivno istraživali 1190 bolesnika s akutnim STEMI liječenih primarnom PCI u osam centara u svim dijelovima Republike Hrvatske (677 netransferiranih, 513 transferiranih). Bolesnici su podijeljeni prema vremenu door-to-balloon u tri podskupine (180 minuta), kao i prema vremenu symptom onset-to-balloon (360 minuta). Između podskupina su uspoređivani postproceduralni TIMI protok, unutarbolnička smrtnost i veliki nepovoljni kardiovaskularni događaji (smrtnost, angina pektoris, restenoza, reinfarkt, aortokoronarno premoštenje i cerebrovaskularni incident) tijekom šestomjesečnog praćenja. Hrvatska mreža primarne PCI osigurava rezultate liječenja akutnog STEMI usporedive s inozemnim randomiziranim studijama i registrima. Između poskupina prema vremenu door-to-balloon niti jedna od rezultatskih razlika nije bila statistički značajna. Između podskupina prema vremenu symptom onset-to-balloon statistički značajna razlika na multivarijatnoj razini bila je ona najviše unutarbolničke smrtnosti u podskupini s najduljim navedenim vremenom (4,5 nasuprot 2,6 nasuprot 5,7%; p=0,04). Vrijeme door-to-balloon je jedna od mjera organizacijske kvalitete mreže primarne PCI i cilj za poboljšanje kvalitete iste, ali bez utjecaja na rane i šestomjesečne rezultate liječenja akutnog STEMI . Vrijeme symptom onset-to-balloon je preciznije za potonje potrebe. Skraćenje vremena symptom onset-to-balloon je, nažalost, složenije nego skraćenje prvoga vremena

Benchmarking of Whole Exome Sequencing and Ad Hoc Designed Panels for Genetic Testing of Hereditary Cancer

Next generation sequencing panels have been developed for hereditary cancer, although there is some debate about their cost-effectiveness compared to exome sequencing. The performance of two panels is compared to exome sequencing. Twenty-four patients were selected: ten with identified mutations (control set) and fourteen suspicious of hereditary cancer but with no mutation (discovery set). TruSight Cancer (94 genes) and a custom panel (122 genes) were assessed alongside exome sequencing. Eightythree genes were targeted by the two panels and exome sequencing. More than 99% of bases had a read depth of over 30x in the panels, whereas exome sequencing covered 94%. Variant calling with standard settings identified the 10 mutations in the control set, with the exception of MSH6 c.255dupC using TruSight Cancer. In the discovery set, 240 unique non-silent coding and canonic splice-site variants were identified in the panel genes, 7 of them putatively pathogenic (in ATM, BARD1, CHEK2, ERCC3, FANCL, FANCM, MSH2). The three approaches identified a similar number of variants in the shared genes. Exomes were more expensive than panels but provided additional data. In terms of cost and depth, panels are a suitable option for genetic diagnostics, although exomes also identify variants in non-targeted genes

Benchmarking of Whole Exome Sequencing and Ad Hoc Designed Panels for Genetic Testing of Hereditary Cancer

Acknowledgements: We thank all patients who contributed to this study. The work was supported by grants from the Instituto de Salud Carlos III (ISCIII, MINECO) (operating grants: PI13/00285 and RD12/0036/0008 awarded to C.L. and PIE13/00022 and RD12/0036/0031 awarded to G.C.) and confunded by FEDER funds/European Regional Development Fund (ERDF) - a way to Build Europe-"// FONDOS FEDER "una manera de hacer Europa", the Generalitat de Catalunya (Government of Catalonia) (operating grant 2014SGR338, awarded to G.C.) and the Asociación Española Contra el Cáncer (operating grants, 2010 Grupos Estables, awarded to G.C.). J.B. received a Spanish Society of Medical Oncology grant. This activity is sponsored by the ISCIII Ministerio de Economía y Competitividad (PT13/0001/0044).Next generation sequencing panels have been developed for hereditary cancer, although there is some debate about their cost-effectiveness compared to exome sequencing. The performance of two panels is compared to exome sequencing. Twenty-four patients were selected: ten with identified mutations (control set) and fourteen suspicious of hereditary cancer but with no mutation (discovery set). TruSight Cancer (94 genes) and a custom panel (122 genes) were assessed alongside exome sequencing. Eightythree genes were targeted by the two panels and exome sequencing. More than 99% of bases had a read depth of over 30x in the panels, whereas exome sequencing covered 94%. Variant calling with standard settings identified the 10 mutations in the control set, with the exception of MSH6 c.255dupC using TruSight Cancer. In the discovery set, 240 unique non-silent coding and canonic splice-site variants were identified in the panel genes, 7 of them putatively pathogenic (in ATM, BARD1, CHEK2, ERCC3, FANCL, FANCM, MSH2). The three approaches identified a similar number of variants in the shared genes. Exomes were more expensive than panels but provided additional data. In terms of cost and depth, panels are a suitable option for genetic diagnostics, although exomes also identify variants in non-targeted genes

Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases

Altres ajuts: Generalitat de Catalunya, Departament de Salut; Generalitat de Catalunya, Departament d'Empresa i Coneixement i CERCA Program; Ministerio de Ciencia e Innovación; Instituto Nacional de Bioinformática; ELIXIR Implementation Studies (CNAG-CRG); Centro de Investigaciones Biomédicas en Red de Enfermedades Raras; Centro de Excelencia Severo Ochoa; European Regional Development Fund (FEDER).Many patients experiencing a rare disease remain undiagnosed even after genomic testing. Reanalysis of existing genomic data has shown to increase diagnostic yield, although there are few systematic and comprehensive reanalysis efforts that enable collaborative interpretation and future reinterpretation. The Undiagnosed Rare Disease Program of Catalonia project collated previously inconclusive good quality genomic data (panels, exomes, and genomes) and standardized phenotypic profiles from 323 families (543 individuals) with a neurologic rare disease. The data were reanalyzed systematically to identify relatedness, runs of homozygosity, consanguinity, single-nucleotide variants, insertions and deletions, and copy number variants. Data were shared and collaboratively interpreted within the consortium through a customized Genome-Phenome Analysis Platform, which also enables future data reinterpretation. Reanalysis of existing genomic data provided a diagnosis for 20.7% of the patients, including 1.8% diagnosed after the generation of additional genomic data to identify a second pathogenic heterozygous variant. Diagnostic rate was significantly higher for family-based exome/genome reanalysis compared with singleton panels. Most new diagnoses were attributable to recent gene-disease associations (50.8%), additional or improved bioinformatic analysis (19.7%), and standardized phenotyping data integrated within the Undiagnosed Rare Disease Program of Catalonia Genome-Phenome Analysis Platform functionalities (18%)

Radial approach to coronary catheterizations and interventions

Radial approach in coronary catheterizations and interventions has been only an alternative of the femoral approach. But due to some important advantages radial approach has a chance to become the first choice in majority of catheterized patients. The most important advantage is the reduction of vascular access site bleeding complications. Additonal benefits are patient satisfaction, cost reduction, shorter hospital stay and possibility of the same-day discharge catheterizations and interventions. The aim of our work was to try to answer three open questions: 1. is it possible to catheterize majority of our patients from the left radial artery when 90% of them are right-handed ? 2. what is the optimal care for the radial artery after the procedure in prevention and treatment of radial artery occlusion? 3. is it effective to implement radial approach in primary PCI as a first approach for STEMI patients? The first part relates the left radial approach. After construction of our special variable support for the left arm and forearm we succesfully used this approach in our studies in almost 90% of patients. The second part of this work contains our randomized trial comparing two different doses of unfractionated heparin in prevention of radial artery occlusion after diagnostic cardiac catheterizations...

Percutaneous technique for creation of tricuspid regurgitation in an ovine model

Experimental models of tricuspid regurgitation (TR) are needed to study the percutaneous placement of prosthetic atrioventricular valves. The purpose of this study was to develop an appropriate simple and reproducible percutaneous experimental model for creation of tricuspid regurgitation. Tricuspid regurgitation was successfully created through papillary muscle avulsion using a guide-wire loop in seven sheep with regurgitation documented on right ventricular angiograms and a significant increase in heart rate and right atrial pressures. Acute onset of tricuspid regurgitation was poorly tolerated in one animal that died. Autopsy examinations showed avulsion of one papillary muscle in four animals and two papillary muscles in three animals