Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF). a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study

Background: Direct-acting oral anticoagulant use for stroke prevention in atrial fibrillation is limited by bleeding concerns. Asundexian, a novel, oral small molecule activated coagulation factor XIa (FXIa) inhibitor, might reduce thrombosis with minimal effect on haemostasis. We aimed to determine the optimal dose of asundexian and to compare the incidence of bleeding with that of apixaban in patients with atrial fibrillation. Methods: In this randomised, double-blind, phase 2 dose-finding study, we compared asundexian 20 mg or 50 mg once daily with apixaban 5 mg twice daily in patients aged 45 years or older with atrial fibrillation, a CHA2DS2-VASc score of at least 2 if male or at least 3 if female, and increased bleeding risk. The study was conducted at 93 sites in 14 countries, including 12 European countries, Canada, and Japan. Participants were randomly assigned (1:1:1) to a treatment group using an interactive web response system, with randomisation stratified by whether patients were receiving a direct-acting oral anticoagulant before the study start. Masking was achieved using a double-dummy design, with participants receiving both the assigned treatment and a placebo that resembled the non-assigned treatment. The primary endpoint was the composite of major or clinically relevant non-major bleeding according to International Society on Thrombosis and Haemostasis criteria, assessed in all patients who took at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT04218266, and EudraCT, 2019-002365-35. Findings: Between Jan 30, 2020, and June 21, 2021, 862 patients were enrolled. 755 patients were randomly assigned to treatment. Two patients (assigned to asundexian 20 mg) never took any study medication, resulting in 753 patients being included in the analysis (249 received asundexian 20 mg, 254 received asundexian 50 g, and 250 received apixaban). The mean age of participants was 73·7 years (SD 8·3), 309 (41%) were women, 216 (29%) had chronic kidney disease, and mean CHA2DS2-VASc score was 3·9 (1·3). Asundexian 20 mg resulted in 81% inhibition of FXIa activity at trough concentrations and 90% inhibition at peak concentrations; asundexian 50 mg resulted in 92% inhibition at trough concentrations and 94% inhibition at peak concentrations. Ratios of incidence proportions for the primary endpoint were 0·50 (90% CI 0·14–1·68) for asundexian 20 mg (three events), 0·16 (0·01–0·99) for asundexian 50 mg (one event), and 0·33 (0·09–0·97) for pooled asundexian (four events) versus apixaban (six events). The rate of any adverse event occurring was similar in the three treatment groups: 118 (47%) with asundexian 20 mg, 120 (47%) with asundexian 50 mg, and 122 (49%) with apixaban. Interpretation: The FXIa inhibitor asundexian at doses of 20 mg and 50 mg once daily resulted in lower rates of bleeding compared with standard dosing of apixaban, with near-complete in-vivo FXIa inhibition, in patients with atrial fibrillation. Funding: Bayer

Surgery and outcome of infective endocarditis in octogenarians: prospective data from the ESC EORP EURO-ENDO registry

Purpose: High mortality and a limited performance of valvular surgery are typical features of infective endocarditis (IE) in octogenarians, even though surgical treatment is a major determinant of a successful outcome in IE. Methods: Data from the prospective multicentre ESC EORP EURO-ENDO registry were used to assess the prognostic role of valvular surgery depending on age. Results: As compared to < 80 yo patients, ≥ 80 yo had lower rates of theoretical indication for valvular surgery (49.1% vs. 60.3%, p < 0.001), of surgery performed (37.0% vs. 75.5%, p < 0.001), and a higher in-hospital (25.9% vs. 15.8%, p < 0.001) and 1-year mortality (41.3% vs. 22.2%, p < 0.001). By multivariable analysis, age per se was not predictive of 1-year mortality, but lack of surgical procedures when indicated was strongly predictive (HR 2.98 [2.43–3.66]). By propensity analysis, 304 ≥ 80 yo were matched to 608 < 80 yo patients. Propensity analysis confirmed the lower rate of indication for valvular surgery (51.3% vs. 57.2%, p = 0.031) and of surgery performed (35.3% vs. 68.4%, p < 0.0001) in ≥ 80 yo. Overall mortality remained higher in ≥ 80 yo (in-hospital: HR 1.50[1.06–2.13], p = 0.0210; 1-yr: HR 1.58[1.21–2.05], p = 0.0006), but was not different from that of < 80 yo among those who had surgery (in-hospital: 19.7% vs. 20.0%, p = 0.4236; 1-year: 27.3% vs. 25.5%, p = 0.7176). Conclusion: Although mortality rates are consistently higher in ≥ 80 yo patients than in < 80 yo patients in the general population, mortality of surgery in ≥ 80 yo is similar to < 80 yo after matching patients. These results confirm the importance of a better recognition of surgical indication and of an increased performance of surgery in ≥ 80 yo patients

Surgery and outcome of infective endocarditis in octogenarians: prospective data from the ESC EORP EURO-ENDO registry

none912Purpose: High mortality and a limited performance of valvular surgery are typical features of infective endocarditis (IE) in octogenarians, even though surgical treatment is a major determinant of a successful outcome in IE. Methods: Data from the prospective multicentre ESC EORP EURO-ENDO registry were used to assess the prognostic role of valvular surgery depending on age. Results: As compared to < 80 yo patients, ≥ 80 yo had lower rates of theoretical indication for valvular surgery (49.1% vs. 60.3%, p < 0.001), of surgery performed (37.0% vs. 75.5%, p < 0.001), and a higher in-hospital (25.9% vs. 15.8%, p < 0.001) and 1-year mortality (41.3% vs. 22.2%, p < 0.001). By multivariable analysis, age per se was not predictive of 1-year mortality, but lack of surgical procedures when indicated was strongly predictive (HR 2.98 [2.43-3.66]). By propensity analysis, 304 ≥ 80 yo were matched to 608 < 80 yo patients. Propensity analysis confirmed the lower rate of indication for valvular surgery (51.3% vs. 57.2%, p = 0.031) and of surgery performed (35.3% vs. 68.4%, p < 0.0001) in ≥ 80 yo. Overall mortality remained higher in ≥ 80 yo (in-hospital: HR 1.50[1.06-2.13], p = 0.0210; 1-yr: HR 1.58[1.21-2.05], p = 0.0006), but was not different from that of < 80 yo among those who had surgery (in-hospital: 19.7% vs. 20.0%, p = 0.4236; 1-year: 27.3% vs. 25.5%, p = 0.7176). Conclusion: Although mortality rates are consistently higher in ≥ 80 yo patients than in < 80 yo patients in the general population, mortality of surgery in ≥ 80 yo is similar to < 80 yo after matching patients. These results confirm the importance of a better recognition of surgical indication and of an increased performance of surgery in ≥ 80 yo patients.nonePazdernik, Michal; Iung, Bernard; Mutlu, Bulent; Alla, François; Riezebos, Robert; Kong, William; Nunes, Maria Carmo Pereira; Pierard, Luc; Srdanovic, Ilija; Yamada, Hirotsugu; De Martino, Andrea; Miglioranza, Marcelo Haertel; Magne, Julien; Piper, Cornelia; Laroche, Cécile; Maggioni, Aldo P; Lancellotti, Patrizio; Habib, Gilbert; Selton-Suty, Christine, EURO-ENDO Investigators group: R Ronderos, G Avegliano, P Fernandez Oses, E Filipini, I Granada, A Iribarren, M Mahia, F Nacinovich, S Ressi, R Obregon, M Bangher, J Dho, L Cartasegna, M L Plastino, V Novas, C Shigel, G Reyes, M De Santos, N Gastaldello, M Granillo Fernandez, M Potito, G Streitenberger, P Velazco, J H Casabé, C Cortes, E Guevara, F Salmo, M Seijo, F Weidinger, M Heger, R Brooks, C Stöllberger, C-Y Ho, L Perschy, L Puskas, G Goliasch, C Binder, R Rosenhek, M Schneider, M-P Winter, E Hoffer, M Melissopoulou, E Lecoq, D Legrand, S Jacquet, M Massoz, P Lancellotti, L Pierard, R Dulgheru, S Marchetta, C D Emal, C Oury, B Cosyns, S Droogmans, D Kerkhove, A Motoc, D Plein, B Roosens, L Soens, C Weytjens, I Lemoine, I Rodrigus, B Paelinck, B Amsel, P Unger, D Konopnicki, C Beauloye, A Pasquet, S Pierard, D Vancraeynest, J L Vanoverschelde, F Sinnaeve, J L Andrade, A C Tude Rodrigues, K Staszko, R Dos Santos Monteiro, M H Miglioranza, D L Shuha, M Alcantara, V Cravo, L Fazzio, A Felix, M Iso, C Musa, A P Siciliano, F Villaca Filho, J Braga, A Rodrigues, R Silva, F Vilela, D Rodrigues, L Silva, S Morhy, C Fischer, R Silva, M Vieira, T Afonso, J Abreu, S N Falcao, V Moises, A Gouvea, G João, F Mancuso, C Silva, A C Souza, C S Abboud, R Bellio de Mattos Barretto, A Ramos, R Arnoni, J E Assef, D J Della Togna, D Le Bihan, L Miglioli, A P Romero Oliveira, R Tadeu Magro Kroll, D Cortez, C L Gelape, M D C Peirira Nunes, T C De Abreu Ferrari, K-L Chan, K Hay, V Le, M Page, F Poulin, C Sauve, K Serri, C Mercure, J Beaudoin, P Pibarot, I Sebag, L Rudski, G Ricafort, B Barsic, V Krajinovic, M Vargovic, J Separovic-Hanzevacki, D Lovric, V Reskovic-Luksic, J Vincelj, S Jaksic Jurinjak, V Yiannikourides, M Ioannides, C Kyriakou, C Pofaides, V Masoura, K Yiangou, J Pudich, A Linhart, M Siranec, J Marek, K Blechova, M Kamenik, M Pazdernik, R Pelouch, Z Coufal, M Mikulica, M Griva, E Jancova, M Mikulcova, M Taborsky, J Precek, M Jecmenova, J Latal, J Widimsky, T Butta, S Machacek, R Vancata, J Spinar, M Holicka, F Pow Chon Long, N Anzules, A Bajana Carpio, G Largacha, E Penaherrera, D Moreira, E Mahfouz, E Elsafty, A Soliman, Y Zayed, J Aboulenein, M Abdel-Hay, A Almaghraby, M Abdelnaby, M Ahmed, B Hammad, Y Saleh, H Zahran, O Elgebaly, A Saad, M Ali, A Zeid, R El Sharkawy, M Meshaal, A Al Kholy, R Doss, D Osama, H Rizk, A Elmogy, M Mishriky, P Assayag, S El Hatimi, Saint- E Botelho-Nevers, S Campisi, J-F Fuzellier, A Gagneux-Brunon, R Pierrard, C Tulane, M Detoc, T Mehalla, D Boutoille, O Al Habash, N Asseray-Madani, C Biron, J Brochard, J Caillon, C Cueff, T Le Tourneau, A S Lecompte, R Lecomte, M Lefebvre, M M Magali Michel, S Pattier, S Delarue, M Le Bras, J Orain, J-F Faucher, V Aboyans, A Beeharry, H Durox, M Lacoste, J Magne, D Mohty, A David, V Pradel, V Sierra, A Neykova, B Bettayeb, S Elkentaoui, B Tzvetkov, G Landry, C Strady, K Ainine, S Baumard, C Brasselet, C Tassigny, V Valente-Pires, M Lefranc, B Hoen, B Lefevre, E Curlier, C Callier, N Fourcade, Y Jobic, S Ansard, R Le Berre, P Le Roux, F Le Ven, M-C Pouliquen, G Prat, F Bouchart, A Savoure, C Alarcon, C Chapuzet, I Gueit, C Tribouilloy, Y Bohbot, F Peugnet, M Gun, B Iung, X Duval, X Lescure, E Ilic-Habensus, N Sadoul, C Selton-Suty, F Alla, E Chevalier, F Goehringer, O Huttin, R Garcia, V Le Marcis, P Tattevin, E Donal, E Flecher, M Revest, G Habib, S Hubert, J-P Casalta, F Gouriet, F Arregle, S Cammilleri, L Tessonnier, A Riberi, C Chirouze, K Bouiller, A-S Brunel, D Fournier, L Hustache-Mathieu, T Klopfenstein, J Moreau, P Lim, L Oliver, J Ternacle, A Moussafeur, P Chavanet, L Piroth, M Buisson, S Mahy, C Martins, A Salmon-Rousseau, S Gohier, C Piper, J Börgermann, D Guckel, D Horstkotte, B Brockmeier, E Winkelmann, A Hagendorff, D Grey, G Nickenig, R Schueler, C Öztürk, E Stöhr, C Hamm, T Walther, R Brandt, A-C Frühauf, C T Hartung, C Hellner, C Wild, M Becker, S Hamada, W Kaestner, K Stangl, F Knebel, G Baldenhofer, A Brecht, H Dreger, C Isner, F Pfafflin, M Stegemann, R Zahn, B Fraiture, C Kilkowski, A-K Karcher, S Klinger, H Tolksdorf, D Tousoulis, C Aggeli, G Sarri, S Sideris, E Venieri, G Athanassopoulos, D Tsiapras, I Armenis, A Koutsiari, G Floros, C Grassos, S Dragasis, L Rallidis, C Varlamos, L Michalis, K Naka, A Bechlioulis, A Kotsia, L Lakkas, K Pappas, C Papadopoulos, S Kiokas, A Lioni, S Misailidou, J Barbetseas, M Bonou, C Kapelios, I Tomprou, K Zerva, A Manolis, E Hamodraka, D Athanasiou, G Haralambidis, L Poulimenos, H Samaras, A Nagy, A Bartykowszki, E Gara, S Sengupta, K Mungulmare, R Kasliwal, M Bansal, A Bhan, S Ranjan, M Kyavar, M Maleki, F Noohi Bezanjani, A Sadeghpour, A Alizadehasl, S Boudagh, A Ghavidel, P Moradnejad, H R Pasha, B Ghadrdoost, D Gilon, J Strahilevitz, S Israel, M Wanounou, C d'Agostino, P Colonna, L De Michele, F Fumarola, M Stante, N Marchionni, V Scheggi, B Alterini, S Del Pace, P Stefano, C Sparano, L P Badano, D Muraru, N Ruozi, R Tenaglia, U Limbruno, A Cresti, P Baratta, M Solari, C Giannattasio, A Moreo, B De Chiara, B Lopez Montero, F Musca, C A Orcese, F Panzeri, C F Russo, F Spano, O Alfieri, M De Bonis, E Agricola, E Busnardo, S Carletti, B Castiglioni, S Chiappetta, B Del Forno, D Ferrara, M Guffanti, G Iaci, E Lapenna, T Nisi, C Oltolini, U Pajoro, R Pasciuta, M Ripa, P Scarpellini, C Tassan Din, R Meneghin, D Schiavi, F Piscione, R Citro, R M Benvenga, L Greco, C Prota, I Radano, L Soriente, M Bellino, D Di Vece, F Santini, A Salsano, G M Olivieri, F Turrini, R Messora, S Tondi, A Olaru, V Agnoletto, L Grassi, C Leonardi, S Sansoni, S Del Ponte, G M Actis Dato, A De Martino, N Ohte, S Kikuchi, K Wakami, K Aonuma, Y Seo, T Ishizu, T Machino-Ohtsuka, M Yamamoto, N Iida, H Nakajima, Y Nakagawa, C Izumi, M Amano, M Miyake, K Takahashi, I Shiojima, Y Miyasaka, H Maeba, Y Suwa, N Taniguchi, S Tsujimoto, T Kitai, M Ota, S Yuda, S Sasaki, N Hagiwara, K Yamazaki, K Ashihara, K Arai, C Saitou, S Saitou, G Suzuki, Y Shibata, N Watanabe, S Nishino, K Ashikaga, N Kuriyama, K Mahara, K Abe, H Fujimaki, T Okubo, H Shitan, S Takanashi, M Terada, H Yamamoto, M Sata, H Yamada, K Kusunose, Y Saijo, H Seno, O Yuichiro, Y Sakata, H Mizuno, S Nakatani, T Onishi, K Sengoku, F Sera, S W Park, K Eun Kyoung, L Ga Yeon, J-W Hwang, C Jin-Oh, S-J Park, L Sang-Chol, C Sung-A, S Y Jang, D-H Kang, R Heo, S Lee, J-M Song, E Jung, J Plisiene, A Dambrauskaite, G Gruodyte, R Jonkaitiene, J Vaskelyte, V Mizariene, J Atkocaityte, R Zvirblyte, R Sow, A Codreanu, E C L De la Vega, C Michaux, T Staub, L Jacobs-Orazi, C Mallia Azzopardi, R G Xuereb, T Piscopo, D Borg, R Casha, J Farrugia, M Fenech, E Pllaha, C Vella, K Yamagata, L Grib, E Raevschi, A Grejdieru, G Balan, I Cardaniuc, L Cardaniuc, V Corcea, A Feodorovici, V Gaina, L Girbu, P Jimbei, D Kravcenco, E Panfile, E Prisacari, E Samohvalov, S Samohvalov, N Sceglova, I Benesco, V Marian, N Sumarga, M Mirocevic, B Bozovic, N Bulatovic, P Lakovic, L Music, J Roos-Hesselink, R Budde, T Gamela, A Wahadat, O Kamp, T Meijers, J P Van Melle, V M Deursen, H Crijns, S Bekkers, E Cheriex, M Gilbers, B Kietselaer, C Knackstedt, R Lorusso, S Schalla, S Streukens, S Chamuleau, M-J Cramer, A Teske, T Van der Spoel, A Wind, O Liesbek, J Lokhorst, H Van Heusden, W Tanis, I Van der Bilt, J Vriend, H De Lange-van Bruggen, E Karijodikoro, R Riezebos, E van Dongen, J Schoep, V Stolk, O Axler, F Baumann, S Lebras, T Edvardsen, J T Offstad, J O Beitnes, T Helle-Valle, H Skulstad, R Skardal, N Qamar, S Furnaz, B Ahmed, M H Butt, M F Khanzada, T Saghir, A Wahid, T Hryniewiecki, P Szymanski, K Marzec, M Misztal-Ogonowska, W Kosmala, M Przewlocka-Kosmala, A Rojek, K Woznicka, J Zachwyc, A Lisowska, M Kaminska, J Kasprzak, E Kowalczyk, D F Strzecka, P Wejner-Mik, M Trabulo, P Freitas, S Ranchordas, G Rodrigues, P Pinto, C Queiros, J Azevedo, L Marques, D Seabra, L Branco, J Abreu, M Cruz, A Galrinho, R Moreira, P Rio, A T Timoteo, M Selas, N M Cardim, V Carmelo, B Duque Neves, H Pereira, I Cruz, A Guerra, A Marques, I Pintassilgo, M C Tomescu, N-M Trofenciuc, M Andor, A Bordejevic, H S Branea, F Caruntu, L Cirin, I M Citu, C A Cotoraci, D Darabantiu, R Farcas, I Marincu, A Mavrea, M F Onel, T Parvanescu, D Pop, A L Pop-Moldovan, M I Puticiu, L A Velcean, A Ionac, D Cozma, C Mornos, F Goanta, I Popescu, R Beyer, R Mada, R Rancea, H Rosianu, R Tomoaia, C Stanescu, Z Kobalava, J Karaulova, E Kotova, A Milto, A Pisaryuk, N Povalyaev, M Sorokina, J Alrahimi, A Elshiekh, A Jamiel, A Ahmed, M Al-Mallah, N Attia, B Putnikovic, A Neskovic, A Dimic, B Ivanovic, S Matic, D Trifunovic, J Petrovic, D Kosevic, P Dabic, P Milojevic, I Petrovic, I Stojanovic, I Srdanovic, M Kovacevic, A Redzek, M Stefanovic, S Susak, L Velicki, A Vulin, T C Yeo, W K F Kong, K K Poh, I Vilacosta, M Abd El- Nasser, C Ferrera, C Olmos, F Calvo Iglesias, E Blanco-Gonzalez, M Bravo Amaro, A N Germinas, E Lopez-Rodriguez, J Lugo Adan, P Pazos-Lopez, M Pereira Loureiro, M T Perez, S Raposeiras-Roubin, S Rasheed Yas, M-M Suarez-Varela, F Vasallo Vidal, D Garcia-Dorado, A Sambola, N Fernandez-Hidalgo, T Gonzalez-Alujas, J Lozano, O Maisterra, N Pizzi, R Rios, P Tornos, A Bayes-Genis, L Pedro Botet, N Vallejo, E Berastegui, C Llibre, L Mateu, R Nunez, D Quesada, D Bosch Portell, J Aboal Vinas, X Albert Bertran, R Brugada Tarradellas, P Loma-Osorio Ricon, C Tiron de Llano, M A Arnau, A Bel, M Blanes, A Osa, M Anguita, F Carrasco, J Castillo, J L Zamorano, J L Moya Mur, M Alvaro, C Fernandez-Golfin, J M Monteagudo, E Navas Elorza, M C Farinas Alvarez, J Aguero Balbin, C Arminanzas, F Arnaiz de Las Revillas, A Arnaiz Garcia, M Cobo Belaustegui, M Fernandez Sampedro, M Gutierrez Cuadra, J F Gutierrez-Diez, J Zarauza, L Garcia Cuello, C Gonzalez Rico, R Rodriguez-Alvarez, J Goikoetxea, M Montejo, J Miro, M Almela, J Ambrosioni, C Falces, D Fuster, C Garcia-de-la-Maria, M Hernandez-Meneses, J Llopis, F Marco, A Moreno, E Quintana, E Sandoval, A Tellez, J M Tolosana, B Vidal, I Ruiz-Zamora, A Bardaji Ruiz, E Sanz Girgas, G Garcia-Pardo, M Guillen Marzo, A Rodriguez Oviedo, A Villares Jimenez, L Abid, R Hammami, S Kammoun, M S Mourali, F Mghaieth Zghal, M Ben Hlima, S Boudiche, S Ouali, L Zakhama, S Antit, I Slama, O Gulel, M Sahin, L E Sade, E Karacaglar, S Kucukoglu, O Cetinarslan, U S Yasar, U Canpolat, B Mutlu, H Atas, R Dervishova, C Ileri, H Zaky, J Alhashmi, F Baslib, J Tahir, P Zarger, S Woldman, L Menezes, C Primus, R Uppal, I Bvekerwa, B Chandrasekaran, A Kopanska, B Prendergast, S Cannata, J Chambers, J Hancock, J Klein, R Rajani, M P Ursi, R Dworakowski, A Fife, J Breeze, M Browne-Morgan, M Gunning, S Streather, F Asch, M Zemedkun, B Alyavi, J UzokovMichal, Pazdernik; Bernard, Iung; Bulent, Mutlu; François, Alla; Robert, Riezebos; William, Kong; Maria Carmo Pereira, Nunes; Luc, Pierard; Ilija, Srdanovic; Hirotsugu, Yamada; Andrea, De Martino; Marcelo Haertel, Miglioranza; Julien, Magne; Cornelia, Piper; Cécile, Laroche; Aldo P, Maggioni; Patrizio, Lancellotti; Gilbert, Habib; Christine, Selton-Suty; R Ronderos, EURO-ENDO Investigators group:; Avegliano, G; Fernandez Oses, P; Filipini, E; Granada, I; Iribarren, A; Mahia, M; Nacinovich, F; Ressi, S; Obregon, R; Bangher, M; Dho, J; Cartasegna, L; L Plastino, M; Novas, V; Shigel, C; Reyes, G; De Santos, M; Gastaldello, N; Granillo Fernandez, M; Potito, M; Streitenberger, G; Velazco, P; H Casabé, J; Cortes, C; Guevara, E; Salmo, F; Seijo, M; Weidinger, F; Heger, M; Brooks, R; Stöllberger, C; Ho, C-Y; Perschy, L; Puskas, L; Goliasch, G; Binder, C; Rosenhek, R; Schneider, M; Winter, M-P; Hoffer, E; Melissopoulou, M; Lecoq, E; Legrand, D; Jacquet, S; Massoz, M; Lancellotti, P; Pierard, L; Dulgheru, R; Marchetta, S; D Emal, C; Oury, C; Cosyns, B; Droogmans, S; Kerkhove, D; Motoc, A; Plein, D; Roosens, B; Soens, L; Weytjens, C; Lemoine, I; Rodrigus, I; Paelinck, B; Amsel, B; Unger, P; Konopnicki, D; Beauloye, C; Pasquet, A; Pierard, S; Vancraeynest, D; L Vanoverschelde, J; Sinnaeve, F; L Andrade, J; C Tude Rodrigues, A; Staszko, K; Dos Santos Monteiro, R; H Miglioranza, M; L Shuha, D; Alcantara, M; Cravo, V; Fazzio, L; Felix, A; Iso, M; Musa, C; P Siciliano, A; Villaca Filho, F; Braga, J; Rodrigues, A; Silva, R; Vilela, F; Rodrigues, D; Silva, L; Morhy, S; Fischer, C; Silva, R; Vieira, M; Afonso, T; Abreu, J; N Falcao, S; Moises, V; Gouvea, A; João, G; Mancuso, F; Silva, C; C Souza, A; S Abboud, C; Bellio de Mattos Barretto, R; Ramos, A; Arnoni, R; E Assef, J; J Della Togna, D; Le Bihan, D; Miglioli, L; P Romero Oliveira, A; Tadeu Magro Kroll, R; Cortez, D; L Gelape, C; C Peirira Nunes, M D; C De Abreu Ferrari, T; Chan, K-L; Hay, K; Le, V; Page, M; Poulin, F; Sauve, C; Serri, K; Mercure, C; Beaudoin, J; Pibarot, P; Sebag, I; Rudski, L; Ricafort, G; Barsic, B; Krajinovic, V; Vargovic, M; Separovic-Hanzevacki, J; Lovric, D; Reskovic-Luksic, V; Vincelj, J; Jaksic Jurinjak, S; Yiannikourides, V; Ioannides, M; Kyriakou, C; Pofaides, C; Masoura, V; Yiangou, K; Pudich, J; Linhart, A; Siranec, M; Marek, J; Blechova, K; Kamenik, M; Pazdernik, M; Pelouch, R; Coufal, Z; Mikulica, M; Griva, M; Jancova, E; Mikulcova, M; Taborsky, M; Precek, J; Jecmenova, M; Latal, J; Widimsky, J; Butta, T; Machacek, S; Vancata, R; Spinar, J; Holicka, M; Pow Chon Long, F; Anzules, N; Bajana Carpio, A; Largacha, G; Penaherrera, E; Moreira, D; Mahfouz, E; Elsafty, E; Soliman, A; Zayed, Y; Aboulenein, J; Abdel-Hay, M; Almaghraby, A; Abdelnaby, M; Ahmed, M; Hammad, B; Saleh, Y; Zahran, H; Elgebaly, O; Saad, A; Ali, M; Zeid, A; El 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Socio-Economic Variations Determine the Clinical Presentation, Aetiology and Outcome of Infective Endocarditis: a Prospective Cohort Study from the ESC-EORP EURO-ENDO (European Infective Endocarditis) Registry

Background: Infective endocarditis (IE) is a life-threatening disease associated with high mortality and morbidity worldwide. We sought to determine how socio-economic factors might influence its epidemiology, clinical presentation, investigation and management, and outcome, in a large international multi-centre registry. Methods: The EurObservationalProgramme (EORP) of the European Society of Cardiology (ESC) EURO-ENDO registry comprises a prospective cohort of 3113 adult patients admitted for IE in 156 hospitals in 40 countries between January 2016 and March 2018. Patients were separated in 3 groups, according to World Bank economic stratification (Group 1 - high income [75.6%]; Group 2 - upper-middle income [15.4%]; Group 3 - lower-middle income [9.1%]). Results: Group 3 patients were younger (median age [IQR]: Group 1 - 66 [53-75] years; Group 2 - 57 [41-68] years; Group 3 - 33 [26-43] years; p<0.001) with a higher frequency of smokers, intravenous drug use and human immunodeficiency virus (HIV) infection (all p<0.001) and presented later (median [IQR) days since symptom onset: Group 1 - 12 [3-35]; Group 2 - 19 [6-54]; Group 3 - 31 [12-62]; p<0.001) with a higher likelihood of developing congestive heart failure (13.6%; 11.1%; and 22.6%, respectively; p<0.001) and persistent fever (9.8%; 14.2%; 27.9%; p<0.001). Among 2157 (69.3%) patients with theoretical indication for cardiac surgery, surgery was performed less frequently in Group 3 patients (75.5%, 76.8% and 51.3%, respectively p<0.001) who also demonstrated the highest mortality (15.0%, 23.0% and 23.7%, respectively; p<0.001). Conclusions: Socio-economic factors influence the clinical profile of patients presenting with IE across the world. Despite younger age, patients from the poorest countries presented with more frequent complications and higher mortality associated with delayed diagnosis and lower use of surgery

Correction to: Surgery and outcome of infective endocarditis in octogenarians: prospective data from the ESC EORP EURO-ENDO registry (Infection, (2022), 50, 5, (1191-1202), 10.1007/s15010-022-01792-0)

In this article the “EURO-ENDO Investigators group” member U. Y. Sinan was incorrectly written as U.S. Yasar. The original article has been corrected

Surgery and outcome of infective endocarditis in octogenarians: prospective data from the ESC EORP EURO-ENDO registry

Purpose: High mortality and a limited performance of valvular surgery are typical features of infective endocarditis (IE) in octogenarians, even though surgical treatment is a major determinant of a successful outcome in IE. Methods: Data from the prospective multicentre ESC EORP EURO-ENDO registry were used to assess the prognostic role of valvular surgery depending on age. Results: As compared to < 80 yo patients, ≥ 80 yo had lower rates of theoretical indication for valvular surgery (49.1% vs. 60.3%, p < 0.001), of surgery performed (37.0% vs. 75.5%, p < 0.001), and a higher in-hospital (25.9% vs. 15.8%, p < 0.001) and 1-year mortality (41.3% vs. 22.2%, p < 0.001). By multivariable analysis, age per se was not predictive of 1-year mortality, but lack of surgical procedures when indicated was strongly predictive (HR 2.98 [2.43–3.66]). By propensity analysis, 304 ≥ 80 yo were matched to 608 < 80 yo patients. Propensity analysis confirmed the lower rate of indication for valvular surgery (51.3% vs. 57.2%, p = 0.031) and of surgery performed (35.3% vs. 68.4%, p < 0.0001) in ≥ 80 yo. Overall mortality remained higher in ≥ 80 yo (in-hospital: HR 1.50[1.06–2.13], p = 0.0210; 1-yr: HR 1.58[1.21–2.05], p = 0.0006), but was not different from that of < 80 yo among those who had surgery (in-hospital: 19.7% vs. 20.0%, p = 0.4236; 1-year: 27.3% vs. 25.5%, p = 0.7176). Conclusion: Although mortality rates are consistently higher in ≥ 80 yo patients than in < 80 yo patients in the general population, mortality of surgery in ≥ 80 yo is similar to < 80 yo after matching patients. These results confirm the importance of a better recognition of surgical indication and of an increased performance of surgery in ≥ 80 yo patients

The ESC-EORP EURO-ENDO (European Infective Endocarditis) registry

Aims: The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) European Endocarditis (EURO-ENDO) registry aims to study the care and outcomes of patients diagnosed with infective endocarditis (IE) and compare findings with recommendations from the 2015 ESC Clinical Practice Guidelines for the management of IE and data from the 2001 Euro Heart Survey. Methods and results: Patients (n = 3116) aged over 18 years with a diagnosis of IE based on the ESC 2015 IE diagnostic criteria were prospectively identified between 1 January 2016 and 31 March 2018. Individual patient data were collected across 156 centres and 40 countries. The primary endpoint is all-cause mortality in hospital and at 1 year. Secondary endpoints are 1-year morbidity (all-cause hospitalization, any cardiac surgery, and IE relapse), the clinical, epidemiological, microbiological, and therapeutic characteristics of patients, the number and timing of non-invasive imaging techniques, and adherence to recommendations as stated in the 2015 ESC Clinical Practice Guidelines for the management of IE. Conclusion: EURO-ENDO is an international registry of care and outcomes of patients hospitalized with IE which will provide insights into the contemporary profile and management of patients with this challenging disease