Clinical utility and prognostic implications of the novel 4S-AF scheme to characterize and evaluate patients with atrial fibrillation: a report from ESC-EHRA EORP-AF Long-Term General Registry
Authors: Ding Wern Yew , Proietti Marco , Boriani Giuseppe , Fauchier Laurent , Blomström-Lundqvist Carina , Marin Francisco , Potpara Tatjana S , Lip Gregory Y H ,   the ESC-EHRA EORP-AF Long-Term General Registry Investigators, Boriani G , Lip G Y H , Tavazzi L , Maggioni A P , Dan G-A , Potpara T , Nabauer M , Marin F , Kalarus Z , Fauchier L , Goda A , Mairesse G , Shalganov T , Antoniades L , Taborsky M , Riahi S , Muda P , García Bolao I , Piot O , Nabauer M , Etsadashvili K , Simantirakis E , Haim M , Azhari A , Najafian J , Santini M , Mirrakhimov E , Kulzida K a , Erglis A , Poposka L , Burg M , Crijns H , Erküner Ö , Atar D , Lenarczyk R , Martins Oliveira M , Shah D , Dan G-A , Serdechnaya E , Potpara T , Diker E , Lip G Y H , Lane D , Zëra E , Ekmekçiu U , Paparisto V , Tase M , Gjergo H , Dragoti J , Goda A , Ciutea M , Ahadi N , el Husseini Z , Raepers M , Leroy J , Haushan P , Jourdan A , Lepiece C , Desteghe L , Vijgen J , Koopman P , Van Genechten G , Heidbuchel H , Boussy T , De Coninck M , Van Eeckhoutte H , Bouckaert N , Friart A , Boreux J , Arend C , Evrard P , Stefan L , Hoffer E , Herzet J , Massoz M , Celentano C , Sprynger M , Pierard L , Melon P , Van Hauwaert B , Kuppens C , Faes D , Van Lier D , Van Dorpe A , Gerardy A , Deceuninck O , Xhaet O , Dormal F , Ballant E , Blommaert D , Yakova D , Hristov M , Yncheva T , Stancheva N , Tisheva S , Tokmakova M , Nikolov F , Gencheva D , Shalganov T , Kunev B , Stoyanov M , Marchov D , Gelev V , Traykov V , Kisheva A , Tsvyatkov H , Shtereva R , Bakalska-Georgieva S , Slavcheva S , Yotov Y , Kubíčková M , Marni Joensen A , Gammelmark A , Hvilsted Rasmussen L , Dinesen P , Riahi S , Krogh Venø S , Sorensen B , Korsgaard A , Andersen K , Fragtrup Hellum C , Svenningsen A , Nyvad O , Wiggers P , May O , Aarup A , Graversen B , Jensen L , Andersen M , Svejgaard M , Vester S , Hansen S , Lynggaard V , Ciudad M , Vettus R , Muda P , Maestre A , Castaño S , Cheggour S , Poulard J , Mouquet V , Leparrée S , Bouet J , Taieb J , Doucy A , Duquenne H , Furber A , Dupuis J , Rautureau J , Font M , Damiano P , Lacrimini M , Abalea J , Boismal S , Menez T , Mansourati J , Range G , Gorka H , Laure C , Vassalière C , Elbaz N , Lellouche N , Djouadi K , Roubille F , Dietz D , Davy J , Granier M , Winum P , Leperchois-Jacquey C , Kassim H , Marijon E , Le Heuzey J , Fedida J , Maupain C , Himbert C , Gandjbakhch E , Hidden-Lucet F , Duthoit G , Badenco N , Chastre T , Waintraub X , Oudihat M , Lacoste J , Stephan C , Bader H , Delarche N , Giry L , Arnaud D , Lopez C , Boury F , Brunello I , Lefèvre M , Mingam R , Haissaguerre M , Le Bidan M , Pavin D , Le Moal V , Leclercq C , Piot O , Beitar T , Martel I , Schmid A , Sadki N , Romeyer-Bouchard C , Da Costa A , Arnault I , Boyer M , Piat C , Fauchier L , Lozance N , Nastevska S , Doneva A , Fortomaroska Milevska B , Sheshoski B , Petroska K , Taneska N , Bakrecheski N , Lazarovska K , Jovevska S , Ristovski V , Antovski A , Lazarova E , Kotlar I , Taleski J , Poposka L , Kedev S , Zlatanovik N , Jordanova S , Bajraktarova Proseva T , Doncovska S , Maisuradze D , Esakia A , Sagirashvili E , Lartsuliani K , Natelashvili N , Gumberidze N , Gvenetadze R , Etsadashvili K , Gotonelia N , Kuridze N , Papiashvili G , Menabde I , Glöggler S , Napp A , Lebherz C , Romero H , Schmitz K , Berger M , Zink M , Köster S , Sachse J , Vonderhagen E , Soiron G , Mischke K , Reith R , Schneider M , Rieker W , Boscher D , Taschareck A , Beer A , Oster D , Ritter O , Adamczewski J , Walter S , Frommhold A , Luckner E , Richter J , Schellner M , Landgraf S , Bartholome S , Naumann R , Schoeler J , Westermeier D , William F , Wilhelm K , Maerkl M , Oekinghaus R , Denart M , Kriete M , Tebbe U , Scheibner T , Gruber M , Gerlach A , Beckendorf C , Anneken L , Arnold M , Lengerer S , Bal Z , Uecker C , Förtsch H , Fechner S , Mages V , Martens E , Methe H , Schmidt T , Schaeffer B , Hoffmann B , Moser J , Heitmann K , Willems S , Willems S , Klaus C , Lange I , Durak M , Esen E , Mibach F , Mibach H , Utech A , Gabelmann M , Stumm R , Ländle V , Gartner C , Goerg C , Kaul N , Messer S , Burkhardt D , Sander C , Orthen R , Kaes S , Baumer A , Dodos F , Barth A , Schaeffer G , Gaertner J , Winkler J , Fahrig A , Aring J , Wenzel I , Steiner S , Kliesch A , Kratz E , Winter K , Schneider P , Haag A , Mutscher I , Bosch R , Taggeselle J , Meixner S , Schnabel A , Shamalla A , Hötz H , Korinth A , Rheinert C , Mehltretter G , Schön B , Schön N , Starflinger A , Englmann E , Baytok G , Laschinger T , Ritscher G , Gerth A , Dechering D , Eckardt L , Kuhlmann M , Proskynitopoulos N , Brunn J , Foth K , Axthelm C , Hohensee H , Eberhard K , Turbanisch S , Hassler N , Koestler A , Stenzel G , Kschiwan D , Schwefer M , Neiner S , Hettwer S , Haeussler-Schuchardt M , Degenhardt R , Sennhenn S , Steiner S , Brendel M , Stoehr A , Widjaja W , Loehndorf S , Logemann A , Hoskamp J , Grundt J , Block M , Ulrych R , Reithmeier A , Panagopoulos V , Martignani C , Bernucci D , Fantecchi E , Diemberger I , Ziacchi M , Biffi M , Cimaglia P , Frisoni J , Boriani G , Giannini I , Boni S , Fumagalli S , Pupo S , Di Chiara A , Mirone P , Fantecchi E , Boriani G , Pesce F , Zoccali C , Malavasi V L , Mussagaliyeva A , Ahyt B , Salihova Z , Koshum-Bayeva K , Kerimkulova A , Bairamukova A , Mirrakhimov E , Lurina B , Zuzans R , Jegere S , Mintale I , Kupics K , Jubele K , Erglis A , Kalejs O , Vanhear K , Burg M , Cachia M , Abela E , Warwicker S , Tabone T , Xuereb R , Asanovic D , Drakalovic D , Vukmirovic M , Pavlovic N , Music L , Bulatovic N , Boskovic A , Uiterwaal H , Bijsterveld N , De Groot J , Neefs J , van den Berg N , Piersma F , Wilde A , Hagens V , Van Es J , Van Opstal J , Van Rennes B , Verheij H , Breukers W , Tjeerdsma G , Nijmeijer R , Wegink D , Binnema R , Said S , Erküner Ö , Philippens S , van Doorn W , Crijns H , Szili-Torok T , Bhagwandien R , Janse P , Muskens A , van Eck M , Gevers R , van der Ven N , Duygun A , Rahel B , Meeder J , Vold A , Holst Hansen C , Engset I , Atar D , Dyduch-Fejklowicz B , Koba E , Cichocka M , Sokal A , Kubicius A , Pruchniewicz E , Kowalik-Sztylc A , Czapla W , Mróz I , Kozlowski M , Pawlowski T , Tendera M , Winiarska-Filipek A , Fidyk A , Slowikowski A , Haberka M , Lachor-Broda M , Biedron M , Gasior Z , Kołodziej M , Janion M , Gorczyca-Michta I , Wozakowska-Kaplon B , Stasiak M , Jakubowski P , Ciurus T , Drozdz J , Simiera M , Zajac P , Wcislo T , Zycinski P , Kasprzak J , Olejnik A , Harc-Dyl E , Miarka J , Pasieka M , Ziemińska-Łuć M , Bujak W , Śliwiński A , Grech A , Morka J , Petrykowska K , Prasał M , Hordyński G , Feusette P , Lipski P , Wester A , Streb W , Romanek J , Woźniak P , Chlebuś M , Szafarz P , Stanik W , Zakrzewski M , Kaźmierczak J , Przybylska A , Skorek E , Błaszczyk H , Stępień M , Szabowski S , Krysiak W , Szymańska M , Karasiński J , Blicharz J , Skura M , Hałas K , Michalczyk L , Orski Z , Krzyżanowski K , Skrobowski A , Zieliński L , Tomaszewska-Kiecana M , Dłużniewski M , Kiliszek M , Peller M , Budnik M , Balsam P , Opolski G , Tymińska A , Ozierański K , Wancerz A , Borowiec A , Majos E , Dabrowski R , Szwed H , Musialik-Lydka A , Leopold-Jadczyk A , Jedrzejczyk-Patej E , Koziel M , Lenarczyk R , Mazurek M , Kalarus Z , Krzemien-Wolska K , Starosta P , Nowalany-Kozielska E , Orzechowska A , Szpot M , Staszel M , Almeida S , Pereira H , Brandão Alves L , Miranda R , Ribeiro L , Costa Carnaxide F , Morgado F , Carmo P , Galvao Santos P , Bernardo R , Adragão P , Ferreira da Silva G , Peres M , Alves M , Leal M , Cordeiro A , Magalhães P , Fontes P , Leão S , Delgado A , Costa A , Marmelo B , Rodrigues B , Moreira D , Santos J , Santos L , Terchet A , Darabantiu D , Mercea S , Turcin Halka V , Pop Moldovan A , Gabor A , Doka B , Catanescu G , Rus H , Oboroceanu L , Bobescu E , Popescu R , Dan A , Buzea A , Daha I , Dan G , Neuhoff I , Baluta M , Ploesteanu R , Dumitrache N , Vintila M , Daraban A , Japie C , Badila E , Tewelde H , Hostiuc M , Frunza S , Tintea E , Bartos D , Ciobanu A , Popescu I , Toma N , Gherghinescu C , Cretu D , Patrascu N , Stoicescu C , Udroiu C , Bicescu G , Vintila V , Vinereanu D , Cinteza M , Rimbas R , Grecu M , Cozma A , Boros F , Ille M , Tica O , Tor R , Corina A , Jeewooth A , Maria B , Georgiana C , Natalia C , Alin D , Dinu-Andrei D , Livia M , Daniela R , Larisa R , Umaar S , Tamara T , Ioachim Popescu M , Nistor D , Sus I , Coborosanu O , Alina-Ramona N , Dan R , Petrescu L , Ionescu G , Popescu I , Vacarescu C , Goanta E , Mangea M , Ionac A , Mornos C , Cozma D , Pescariu S , Solodovnicova E , Soldatova I , Shutova J , Tjuleneva L , Zubova T , Uskov V , Obukhov D , Rusanova G , Soldatova I , Isakova N , Odinsova S , Arhipova T , Kazakevich E , Serdechnaya E , Zavyalova O , Novikova T , Riabaia I , Zhigalov S , Drozdova E , Luchkina I , Monogarova Y , Hegya D , Rodionova L , Rodionova L , Nevzorova V , Soldatova I , Lusanova O , Arandjelovic A , Toncev D , Vukmirovic L , Radisavljevic M , Milanov M , Sekularac N , Zdravkovic M , Hinic S , Dimkovic S , Acimovic T , Saric J , Radovanovic S , Kocijancic A , Obrenovic-Kircanski B , Kalimanovska Ostric D , Simic D , Jovanovic I , Petrovic I , Polovina M , Vukicevic M , Tomasevic M , Mujovic N , Radivojevic N , Petrovic O , Aleksandric S , Kovacevic V , Mijatovic Z , Ivanovic B , Tesic M , Potpara T , Ristic A , Vujisic-Tesic B , Nedeljkovic M , Karadzic A , Uscumlic A , Prodanovic M , Zlatar M , Asanin M , Bisenic B , Vasic V , Popovic Z , Djikic D , Sipic M , Peric V , Dejanovic B , Milosevic N , Backovic S , Stevanovic A , Andric A , Pencic B , Pavlovic-Kleut M , Celic V , Pavlovic M , Petrovic M , Vuleta M , Petrovic N , Simovic S , Savovic Z , Milanov S , Davidovic G , Iric-Cupic V , Djordjevic D , Damjanovic M , Zdravkovic S , Topic V , Stanojevic D , Randjelovic M , Jankovic-Tomasevic R , Atanaskovic V , Antic S , Pavlovic M , Simonovic D , Stojanovic M , Stojanovic S , Mitic V , Ilic V , Petrovic D , Deljanin Ilic M , Ilic S , Stoickov V , Mijatovic S. A , Tanasic D , Petrovic D , Radakovic G , Peranovic J , Pavlovic M , Panic-Jelic N , Vujadinovic O , Pajic P , Bekic S , Kovacevic S , García Fernandez A , Perez Cabeza A , Anguita M , Tercedor Sanchez L , Mau E , Loayssa J , Ayarra M , Carpintero M , Roldán Rabadan I , Leal M , Gil Ortega M , Tello Montoliu A , Orenes Piñero E , Manzano Fernández S , Marín F , Romero Aniorte A , Veliz Martínez A , Quintana Giner M , Ballesteros G , Palacio M , Alcalde O , García-Bolao I , Bertomeu Gonzalez V , Otero-Raviña F , García Seara J , Gonzalez Juanatey J , Dayal N , Maziarski P , Gentil-Baron P , Shah D , Koç M , Onrat E , Dural I E , Yilmaz K , Özin B , Tan Kurklu S , Atmaca Y , Canpolat U , Tokgozoglu L , Dolu A K , Demirtas B , Sahin D , Ozcan Celebi O , Diker E , Gagirci G , Turk U O , Ari H , Polat N , Toprak N , Sucu M , Akin Serdar O , Taha Alper A , Kepez A , Yuksel Y , Uzunselvi A , Yuksel S , Sahin M , Ozcan O T , Kaya H , Yilmaz M B , Kutlu M , Demir M , Gibbs C , Kaminskiene S , Bryce M , Skinner A , Belcher G , Hunt J , Stancombe L , Holbrook B , Peters C , Tettersell S , Shantsila A , Lane D , Senoo K , Proietti M , Russell K , Domingos P , Hussain S , Partridge J , Haynes R , Bahadur S , Brown R , McMahon S , Lip G Y H , McDonald J , Balachandran K , Singh R , Garg S , Desai H , Davies K , Goddard W , Galasko G , Rahman I , Chua Y , Payne O , Preston S , Brennan O , Pedley L , Whiteside C , Dickinson C , Brown J , Jones K , Benham L , Brady R , Buchanan L , Ashton A , Crowther H , Fairlamb H , Thornthwaite S , Relph C , McSkeane A , Poultney U , Kelsall N , Rice P , Wilson T , Wrigley M , Kaba R , Patel T , Young E , Law J , Runnett C , Thomas H , McKie H , Fuller J , Pick S , Sharp A , Hunt A , Thorpe K , Hardman C , Cusack E , Adams L , Hough M , Keenan S , Bowring A , Watts J , Zaman J , Goffin K , Nutt H , Beerachee Y , Featherstone J , Mills C , Pearson J , Stephenson L , Grant S , Wilson A , Hawksworth C , Alam I , Robinson M , Ryan S , Egdell R , Gibson E , Holland M , Leonard D , Mishra B , Ahmad S , Randall H , Hill J , Reid L , George M , McKinley S , Brockway L , Milligan W , Sobolewska J , Muir J , Tuckis L , Winstanley L , Jacob P , Kaye S , Morby L , Jan A , Sewell T , Boos C , Wadams B , Cope C , Jefferey P , Andrews N , Getty A , Suttling A , Turner C , Hudson K , Austin R , Howe S , Iqbal R , Gandhi N , Brophy K , Mirza P , Willard E , Collins S , Ndlovu N , Subkovas E , Karthikeyan V , Waggett L , Wood A , Bolger A , Stockport J , Evans L , Harman E , Starling J , Williams L , Saul V , Sinha M , Bell L , Tudgay S , Kemp S , Brown J , Frost L , Ingram T , Loughlin A , Adams C , Adams M , Hurford F , Owen C , Miller C , Donaldson D , Tivenan H , Button H , Nasser A , Jhagra O , Stidolph B , Brown C , Livingstone C , Duffy M , Madgwick P , Roberts P , Greenwood E , Fletcher L , Beveridge M , Earles S , McKenzie D , Beacock D , Dayer M , Seddon M , Greenwell D , Luxton F , Venn F , Mills H , Rewbury J , James K , Roberts K , Tonks L , Felmeden D , Taggu W , Summerhayes A , Hughes D , Sutton J , Felmeden L , Khan M , Walker E , Norris L , O'Donohoe L , Mozid A , Dymond H , Lloyd-Jones H , Saunders G , Simmons D , Coles D , Cotterill D , Beech S , Kidd S , Wrigley B , Petkar S , Smallwood A , Jones R , Radford E , Milgate S , Metherell S , Cottam V , Buckley C , Broadley A , Wood D , Allison J , Rennie K , Balian L , Howard L , Pippard L , Board S , Pitt-Kerby T 
Published: October 2021

Abstract

Aims
The 4S-AF classification scheme comprises of four domains: stroke risk (St), symptoms (Sy), severity of atrial fibrillation (AF) burden (Sb), and substrate (Su). We sought to examine the implementation of the 4S-AF scheme in the EORP-AF General Long-Term Registry and compare outcomes in AF patients according to the 4S-AF-led decision-making process.

Methods and results
Atrial fibrillation patients from 250 centres across 27 European countries were included. A 4S-AF score was calculated as the sum of each domain with a maximum score of 9. Of 6321 patients, 8.4% had low (St), 47.5% EHRA I (Sy), 40.5% newly diagnosed or paroxysmal AF (Sb), and 5.1% no cardiovascular risk factors or left atrial enlargement (Su). Median follow-up was 24 months. Using multivariable Cox regression analysis, independent predictors of all-cause mortality were (St) [adjusted hazard ratio (aHR) 8.21, 95% confidence interval (CI): 2.60–25.9], (Sb) (aHR 1.21, 95% CI: 1.08–1.35), and (Su) (aHR 1.27, 95% CI: 1.14–1.41). For CV mortality and any thromboembolic event, only (Su) (aHR 1.73, 95% CI: 1.45–2.06) and (Sy) (aHR 1.29, 95% CI: 1.00–1.66) were statistically significant, respectively. None of the domains were independently linked to ischaemic stroke or major bleeding. Higher 4S-AF score was related to a significant increase in all-cause mortality, CV mortality, any thromboembolic event, and ischaemic stroke but not major bleeding. Treatment of all 4S-AF domains was associated with an independent decrease in all-cause mortality (aHR 0.71, 95% CI: 0.55–0.92). For each 4S-AF domain left untreated, the risk of all-cause mortality increased substantially (aHR 1.35, 95% CI: 1.16–1.56).

Conclusion
Implementation of the novel 4S-AF scheme is feasible, and treatment decisions based on this scheme improve mortality rates in AF.