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Intracellular calcium leak in heart failure and atrial fibrillation: a unifying mechanism and therapeutic target
Dridi, Haikel; Kushnir, Alexander; Zalk, Ran; Yuan, Qi; Melville, Zephan; Marks, Andrew R
Ca2+ is a fundamental second messenger in all cell types and is required for numerous essential cellular functions, including cardiac and skeletal muscle contraction. The intracellular concentration of free Ca2+ ([Ca2+]) is regulated primarily by ion channels, pumps (ATPases), exchangers and Ca2+-binding proteins. Defective regulation of [Ca2+] is found in a diverse spectrum of pathological states that affect all the major organs. In the heart, abnormalities in the regulation of cytosolic and mitochondrial [Ca2+] occur in heart failure (HF) and atrial fibrillation (AF), two common forms of heart disease and leading contributors to morbidity and mortality. In this Review, we focus on the mechanisms that regulate ryanodine receptor 2 (RYR2), the major sarcoplasmic reticulum (SR) Ca2+-release channel in the heart, how RYR2 becomes dysfunctional in HF and AF, and its potential as a therapeutic target. Inherited RYR2 mutations and/or stress-induced phosphorylation and oxidation of the protein destabilize the closed state of the channel, resulting in a pathological diastolic Ca2+ leak from the SR that both triggers arrhythmias and impairs contractility. On the basis of our increased understanding of SR Ca2+ leak as a shared Ca2+-dependent pathological mechanism in HF and AF, a new class of drugs developed in our laboratory, known as rycals, which stabilize RYR2 channels and prevent Ca2+ leak from the SR, are undergoing investigation in clinical trials.
PMID: 32555383
ISSN: 1759-5010
CID: 4552722
Cardiac electrophysiology consultative experience at the epicenter of the COVID-19 pandemic in the United States
Berman, Jeremy P; Abrams, Mark P; Kushnir, Alexander; Rubin, Geoffrey A; Ehlert, Frederick; Biviano, Angelo; Morrow, John P; Dizon, Jose; Wan, Elaine Y; Yarmohammadi, Hirad; Waase, Marc P; Rubin, David A; Garan, Hasan; Saluja, Deepak
BACKGROUND:The COVID-19 pandemic has greatly altered the practice of cardiac electrophysiology around the world for the foreseeable future. Professional organizations have provided guidance for practitioners, but real-world examples of the consults and responsibilities cardiac electrophysiologists face during a surge of COVID-19 patients is lacking. METHODS:In this observational case series we report on 29 consecutive inpatient electrophysiology consultations at a major academic medical center in New York City, the epicenter of the pandemic in the United States, during a 2 week period from March 30-April 12, 2020, when 80% of hospital beds were occupied by COVID-19 patients, and the New York City metropolitan area accounted for 10% of COVID-19 cases worldwide. RESULTS:Reasons for consultation included: Atrial tachyarrhythmia (31%), cardiac implantable electronic device management (28%), bradycardia (14%), QTc prolongation (10%), ventricular arrhythmia (7%), post-transcatheter aortic valve replacement conduction abnormality (3.5%), ventricular pre-excitation (3.5%), and paroxysmal supraventricular tachycardia (3.5%). Twenty-four patients (86%) were positive for COVID-19 by nasopharyngeal swab. All elective procedures were canceled, and only one urgent device implantation was performed. Thirteen patients (45%) required in-person evaluation and the remainder were managed remotely. CONCLUSION/CONCLUSIONS:Our experience shows that the application of a massive alteration in workflow and personnel forced by the pandemic allowed our team to efficiently address the intersection of COVID-19 with a range of electrophysiology issues. This experience will prove useful as guidance for emerging hot spots or areas affected by future waves of the pandemic.
PMCID:7450949
PMID: 32861812
ISSN: 0972-6292
CID: 4587672
Left atrial wall thickness correlates with pulmonary vein reconnection following atrial fibrillation ablation
Kushnir, Alexander; Barbhaiya, Chirag R; Jankelson, Lior; Holmes, Douglas; Aizer, Anthony; Park, David; Bernstein, Scott; Spinelli, Michael A; Garber, Leonid; Yang, Felix; Rosinski, Elizabeth; Chinitz, Larry A
BACKGROUND:Pulmonary vein (PV) isolation is the cornerstone of radiofrequency (RF) ablation for atrial fibrillation (AF) and PV reconnection is a common cause of recurrent AF. The relationship between PV ostial wall thickness (WT) and durable PV isolation is a matter of ongoing investigation. Additionally, the relationship between catheter impedance and WT is not well understood. We studied the relationship between PV ostial WT, ablation lesion metrics, and PV reconnection. METHODS:16 patients were identified who underwent an initial and redo AF ablation procedure and had a cardiac CTA analyzed using ADAS-3D imaging software performed prior to the initial ablation. Ablation lesion metrics from the initial ablation procedure were collected from the electroanatomic mapping software. Reconnected and isolated PV were identified based on electroanatomic mapping data collected at the redo AF ablation procedure. Patients with reconnected PV exhibited thicker left atrial walls (1.4 mm vs 1.2 mm, P < 0.05) and reconnected veins exhibited thicker ostial walls (1.7 mm, vs 1.5 mm, P < 0.05). LA volume, number of ablation lesions, and ablation lesion time were not significantly different between reconnected and isolated PV. Impedance drop during ablation was greater in patients with reconnected PV compared to patients with isolated PV (- 9.0 Ω vs - 6.6 Ω, P < 0.05). There was no correlation between PV ostial WT and ablation lesion impedance drop. CONCLUSION/CONCLUSIONS:PV reconnection was associated with thicker LA and PV ostial WT. Future studies will examine whether targeting thicker PV ostial tissue with more aggressive lesion metrics or different ablation technology can improve PV isolation and ablationoutcomes.
PMID: 40542289
ISSN: 1572-8595
CID: 5871412
Peak Frequency Analysis Distinguishes Nearfield from Farfield Signals during Pulmonary Vein Isolation
Ting, Peter; Barbhaiya, Chirag R; Jankelson, Lior; Holmes, Douglas; Kushnir, Alexander; Yang, Felix; Bernstein, Scott A; Park, David S; Chinitz, Larry A; Aizer, Anthony
BACKGROUND:Identifying nearfield and farfield signals is critical to mapping and ablating cardiac arrhythmias. This assessment is qualitative, depending on the "sharpness" of pulmonary vein (PV) electrograms. Electrogram peak frequency (PF) analysis is hypothesized to be a quantitative measure of signal proximity. OBJECTIVE:To confirm if PF defines nearfield versus farfield electrical signals and if it can be used during ablation to establish pulmonary vein isolation (PVI). METHODS:We created a cohort of 30 patients with AF undergoing PVI. Left atrial and PV maps of PF were generated before and after PVI. In the first 10 patients with paroxysmal AF (cohort 1), a cutoff value was selected to predict nearfield versus farfield signals. This cutoff was validated in a cohort of 10 patients with paroxysmal AF (cohort 2) and a cohort of 10 patients with persistent AF (cohort 3). RESULTS:PF was lower in farfield electrograms than nearfield electrograms. A PF cutoff of 300 Hz had a sensitivity of 93.2% (95% CI 81.3% - 98.6%) in cohort 1, 90.0% (95% CI 76.3 - 97.2) in cohort 2, and 98.6% (95% CI 90.1 - 99.7%) in cohort 3 for differentiating farfield from nearfield electrograms. The specificity was 100.0% (95% CI 98.2% - 100.0%) and the AUC was 0.99 (95% CI 0.97 - 1.00) in all patients. CONCLUSIONS:We confirmed the hypothesis that PF distinguishes nearfield from farfield electrograms. PF analysis improves the recognition of PV isolation. Mapping and ablation strategies utilizing PF should be pursued to improve ablation outcomes.
PMID: 40480589
ISSN: 1556-3871
CID: 5862902
Persistent Left Atrial Appendage Thrombus in Atrial Fibrillation Despite Anticoagulation
Kushnir, Alexander; Bernstein, Scott; Barbhaiya, Chirag R; Jankelson, Lior; Holmes, Douglas; Aizer, Anthony; Park, David; Spinelli, Michael; Garber, Leonard; Yang, Felix; Chinitz, Larry A
OBJECTIVES/OBJECTIVE:Assess the characteristics and management of patients with LAA thrombus despite compliance with oral anticoagulation (OAC). BACKGROUND:Atrial fibrillation guidelines consider 4 weeks of uninterrupted OAC sufficient to avoid transesophageal echocardiography to rule out left atrial appendage thrombus. However, some patients may exhibit persistent thrombus despite compliance with OAC. METHODS:Clinical history, management, and outcomes were reviewed for patients with LAA thrombus on preprocedural TEE presenting for an AF related procedure between 2021 and 2024. RESULTS:Sixty-five (1.8%) of 3653 preprocedural TEEs exhibited LAA thrombus. OAC compliance of at least 4 week was documented in 39 (60%) of these patients, including Apixaban 64%, Rivaroxaban 23%, Warfarin 8%, Dabigatran 5%. Two of these patients (3%) experienced an embolic event and 8 (12%) died during the follow up period. Resolution of LAA thrombus was documented in 12/32 patients, 6 who switched to Dabigatran, 2 to Eliquis, 1 to Warfarin, and 3 remained on Eliquis. LAA-occlusion was successfully performed in seven patients with persistent LAA thrombus. CHADS-VASc 3 or greater, HFrEF, or valvular AF were present in 37/39 of these patients. CONCLUSION/CONCLUSIONS:For 3653 patients who underwent Preprocedural TEE, 39 exhibited LAA thrombus despite compliance with OAC. Switching OAC or maintaining the same agent for longer period of time resolved the thrombus in 31% of cases. LAA-O was effective in cases where the thrombus did not resolve. Patients with non-valvular AF, compliance with OAC > 4 weeks, CHADS-VASc ≤ 2, and normal EF exhibited the lowest probability for not having a thrombus on TEE.
PMID: 40371618
ISSN: 1540-8167
CID: 5844522
Quantitative considerations for choosing between Amulet and Watchman FLX and management of device related complications
Kushnir, Alexander; Barbhaiya, Chirag R; Jankelson, Lior; Holmes, Douglas; Aizer, Anthony; Park, David; Spinelli, Michael; Bernstein, Scott; Garber, Leonard; Yang, Felix; Ro, Richard; Chinitz, Larry A
BACKGROUND:Left atrial appendage occlusion (LAA-O) with Amulet and Watchman FLX are approved for reducing stroke risk in patients with atrial fibrillation when oral anticoagulation is not tolerated. Real world clinical outcomes reported along with imaging data are needed to help clinicians choose between these two technologies and manage device-related complications. METHODS:The study retrospectively analyzed clinical, transesophageal (TEE), and available computed tomography (CT) data from 364 FLX and 292 Amulet procedures performed at an academic medical center over a 4-year period. RESULTS:were included. TTE LAA-orifice area correlated with CT-derived measurements. There were more late pericardial effusions for Amulet (3.1%) compared to FLX (0.3%), though the majority were conservatively managed. Mean procedure times were similar (FLX 64 ± 24, Amulet 65 ± 21 min) as were the rates of device related thrombus (FLX 1% and Amulet 1.4%). Clinically relevant peridevice leak (PDL) on follow-up TEE imaging was greater for FLX (16%) compared to Amulet (10%). Combined AF ablation-LAA-occlusion procedures exhibited lower rates of PDL and late pericardial effusions compared to solo procedures. CONCLUSIONS:Based on retrospective analysis, an initial strategy with Watchman FLX in patients with favorable LAA anatomy would reduce the risk of late pericardial effusions at the expense of a higher rate of clinically relevant PDL compared to Amulet. Combined AF ablation and LAA-O procedures exhibit less PDL.
PMID: 39939509
ISSN: 1572-8595
CID: 5793662
AI is a viable alternative to high throughput screening: a 318-target study
Wallach, Izhar; Bernard, Denzil; Nguyen, Kong; Ho, Gregory; Morrison, Adrian; Stecula, Adrian; Rosnik, Andreana; O"™Sullivan, Ann Marie; Davtyan, Aram; Samudio, Ben; Thomas, Bill; Worley, Brad; Butler, Brittany; Laggner, Christian; Thayer, Desiree; Moharreri, Ehsan; Friedland, Greg; Truong, Ha; van den Bedem, Henry; Ng, Ho Leung; Stafford, Kate; Sarangapani, Krishna; Giesler, Kyle; Ngo, Lien; Mysinger, Michael; Ahmed, Mostafa; Anthis, Nicholas J.; Henriksen, Niel; Gniewek, Pawel; Eckert, Sam; de Oliveira, Saulo; Suterwala, Shabbir; PrasadPrasad, Srimukh Veccham Krishna; Shek, Stefani; Contreras, Stephanie; Hare, Stephanie; Palazzo, Teresa; O"™Brien, Terrence E.; Van Grack, Tessa; Williams, Tiffany; Chern, Ting Rong; Kenyon, Victor; Lee, Andreia H.; Cann, Andrew B.; Bergman, Bastiaan; Anderson, Brandon M.; Cox, Bryan D.; Warrington, Jeffrey M.; Sorenson, Jon M.; Goldenberg, Joshua M.; Young, Matthew A.; DeHaan, Nicholas; Pemberton, Ryan P.; Schroedl, Stefan; Abramyan, Tigran M.; Gupta, Tushita; Mysore, Venkatesh; Presser, Adam G.; Ferrando, Adolfo A.; Andricopulo, Adriano D.; Ghosh, Agnidipta; Ayachi, Aicha Gharbi; Mushtaq, Aisha; Shaqra, Ala M.; Toh, Alan Kie Leong; Smrcka, Alan V.; Ciccia, Alberto; de Oliveira, Aldo Sena; Sverzhinsky, Aleksandr; de Sousa, Alessandra Mara; Agoulnik, Alexander I.; Kushnir, Alexander; Freiberg, Alexander N.; Statsyuk, Alexander V.; Gingras, Alexandre R.; Degterev, Alexei; Tomilov, Alexey; Vrielink, Alice; Garaeva, Alisa A.; Bryant-Friedrich, Amanda; Caflisch, Amedeo; Patel, Amit K.; Rangarajan, Amith Vikram; Matheeussen, An; Battistoni, Andrea; Caporali, Andrea; Chini, Andrea; Ilari, Andrea; Mattevi, Andrea; Foote, Andrea Talbot; Trabocchi, Andrea; Stahl, Andreas; Herr, Andrew B.; Berti, Andrew; Freywald, Andrew; Reidenbach, Andrew G.; Lam, Andrew; Cuddihy, Andrew R.; White, Andrew; Taglialatela, Angelo; Ojha, Anil K.; Cathcart, Ann M.; Motyl, Anna A.L.; Borowska, Anna; D"™Antuono, Anna; Hirsch, Anna K.H.; Porcelli, Anna Maria; Minakova, Anna; Montanaro, Anna; Müller, Anna; Fiorillo, Annarita; Virtanen, Anniina; O"™Donoghue, Anthony J.; Del Rio Flores, Antonio; Garmendia, Antonio E.; Pineda-Lucena, Antonio; Panganiban, Antonito T.; Samantha, Ariela; Chatterjee, Arnab K.; Haas, Arthur L.; Paparella, Ashleigh S.; John, Ashley L.St; Prince, Ashutosh; ElSheikh, Assmaa; Apfel, Athena Marie; Colomba, Audrey; O"™Dea, Austin; Diallo, Bakary N"™tji; Ribeiro, Beatriz Murta Rezende Moraes; Bailey-Elkin, Ben A.; Edelman, Benjamin L.; Liou, Benjamin; Perry, Benjamin; Chua, Benjamin Soon Kai; Kováts, Benjámin; Englinger, Bernhard; Balakrishnan, Bijina; Gong, Bin; Agianian, Bogos; Pressly, Brandon; Salas, Brenda P.Medellin; Duggan, Brendan M.; Geisbrecht, Brian V.; Dymock, Brian W.; Morten, Brianna C.; Hammock, Bruce D.; Mota, Bruno Eduardo Fernandes; Dickinson, Bryan C.; Fraser, Cameron; Lempicki, Camille; Novina, Carl D.; Torner, Carles; Ballatore, Carlo; Bon, Carlotta; Chapman, Carly J.; Partch, Carrie L.; Chaton, Catherine T.; Huang, Chang; Yang, Chao Yie; Kahler, Charlene M.; Karan, Charles; Keller, Charles; Dieck, Chelsea L.; Huimei, Chen; Liu, Chen; Peltier, Cheryl; Mantri, Chinmay Kumar; Kemet, Chinyere Maat; Müller, Christa E.; Weber, Christian; Zeina, Christina M.; Muli, Christine S.; Morisseau, Christophe; Alkan, Cigdem; Reglero, Clara; Loy, Cody A.; Wilson, Cornelia M.; Myhr, Courtney; Arrigoni, Cristina; Paulino, Cristina; Santiago, César; Luo, Dahai; Tumes, Damon J.; Keedy, Daniel A.; Lawrence, Daniel A.; Chen, Daniel; Manor, Danny; Trader, Darci J.; Hildeman, David A.; Drewry, David H.; Dowling, David J.; Hosfield, David J.; Smith, David M.; Moreira, David; Siderovski, David P.; Shum, David; Krist, David T.; Riches, David W.H.; Ferraris, Davide Maria; Anderson, Deborah H.; Coombe, Deirdre R.; Welsbie, Derek S.; Hu, Di; Ortiz, Diana; Alramadhani, Dina; Zhang, Dingqiang; Chaudhuri, Dipayan; Slotboom, Dirk J.; Ronning, Donald R.; Lee, Donghan; Dirksen, Dorian; Shoue, Douglas A.; Zochodne, Douglas William; Krishnamurthy, Durga; Duncan, Dustin; Glubb, Dylan M.; Gelardi, Edoardo Luigi Maria; Hsiao, Edward C.; Lynn, Edward G.; Silva, Elany Barbosa; Aguilera, Elena; Lenci, Elena; Abraham, Elena Theres; Lama, Eleonora; Mameli, Eleonora; Leung, Elisa; Christensen, Emily M.; Mason, Emily R.; Petretto, Enrico; Trakhtenberg, Ephraim F.; Rubin, Eric J.; Strauss, Erick; Thompson, Erik W.; Cione, Erika; Lisabeth, Erika Mathes; Fan, Erkang; Kroon, Erna Geessien; Jo, Eunji; Garcia-Cuesta, Eva M.; Glukhov, Evgenia; Gavathiotis, Evripidis; Yu, Fang; Xiang, Fei; Leng, Fenfei; Wang, Feng; Ingoglia, Filippo; van den Akker, Focco; Borriello, Francesco; Vizeacoumar, Franco J.; Luh, Frank; Buckner, Frederick S.; Vizeacoumar, Frederick S.; Bdira, Fredj Ben; Svensson, Fredrik; Rodriguez, G. Marcela; Bognár, Gabriella; Lembo, Gaia; Zhang, Gang; Dempsey, Garrett; Eitzen, Gary; Mayer, Gaétan; Greene, Geoffrey L.; Garcia, George A.; Lukacs, Gergely L.; Prikler, Gergely; Parico, Gian Carlo G.; Colotti, Gianni; De Keulenaer, Gilles; Cortopassi, Gino; Roti, Giovanni; Girolimetti, Giulia; Fiermonte, Giuseppe; Gasparre, Giuseppe; Leuzzi, Giuseppe; Dahal, Gopal; Michlewski, Gracjan; Conn, Graeme L.; Stuchbury, Grant David; Bowman, Gregory R.; Popowicz, Grzegorz Maria; Veit, Guido; de Souza, Guilherme Eduardo; Akk, Gustav; Caljon, Guy; Alvarez, Guzmán; Rucinski, Gwennan; Lee, Gyeongeun; Cildir, Gokhan; Li, Hai; Breton, Hairol E.; Jafar-Nejad, Hamed; Zhou, Han; Moore, Hannah P.; Tilford, Hannah; Yuan, Haynes; Shim, Heesung; Wulff, Heike; Hoppe, Heinrich; Chaytow, Helena; Tam, Heng Keat; Van Remmen, Holly; Xu, Hongyang; Debonsi, Hosana Maria; Lieberman, Howard B.; Jung, Hoyoung; Fan, Hua Ying; Feng, Hui; Zhou, Hui; Kim, Hyeong Jun; Greig, Iain R.; Caliandro, Ileana; Corvo, Ileana; Arozarena, Imanol; Mungrue, Imran N.; Verhamme, Ingrid M.; Qureshi, Insaf Ahmed; Lotsaris, Irina; Cakir, Isin; Perry, J. Jefferson P.; Kwiatkowski, Jacek; Boorman, Jacob; Ferreira, Jacob; Fries, Jacob; Kratz, Jadel Müller; Miner, Jaden; Siqueira-Neto, Jair L.; Granneman, James G.; Ng, James; Shorter, James; Voss, Jan Hendrik; Gebauer, Jan M.; Chuah, Janelle; Mousa, Jarrod J.; Maynes, Jason T.; Evans, Jay D.; Dickhout, Jeffrey; MacKeigan, Jeffrey P.; Jossart, Jennifer N.; Zhou, Jia; Lin, Jiabei; Xu, Jiake; Wang, Jianghai; Zhu, Jiaqi; Liao, Jiayu; Xu, Jingyi; Zhao, Jinshi; Lin, Jiusheng; Lee, Jiyoun; Reis, Joana; Stetefeld, Joerg; Bruning, John B.; , ; Coles, John G.; Tanner, John J.; Pascal, John M.; So, Jonathan; Pederick, Jordan L.; Costoya, Jose A.; Rayman, Joseph B.; Maciag, Joseph J.; Nasburg, Joshua Alexander; Gruber, Joshua J.; Finkelstein, Joshua M.; Watkins, Joshua; Rodriguez-Frade, José Miguel; Arias, Juan Antonio Sanchez; Lasarte, Juan José; Oyarzabal, Julen; Milosavljevic, Julian; Cools, Julie; Lescar, Julien; Bogomolovas, Julijus; Wang, Jun; Kee, Jung Min; Kee, Jung Min; Liao, Junzhuo; Sistla, Jyothi C.; Abrahão, Jônatas Santos; Sishtla, Kamakshi; Francisco, Karol R.; Hansen, Kasper B.; Molyneaux, Kathleen A.; Cunningham, Kathryn A.; Martin, Katie R.; Gadar, Kavita; Ojo, Kayode K.; Wong, Keith S.; Wentworth, Kelly L.; Lai, Kent; Lobb, Kevin A.; Hopkins, Kevin M.; Parang, Keykavous; Machaca, Khaled; Pham, Kien; Ghilarducci, Kim; Sugamori, Kim S.; McManus, Kirk James; Musta, Kirsikka; Faller, Kiterie M.E.; Nagamori, Kiyo; Mostert, Konrad J.; Korotkov, Konstantin V.; Liu, Koting; Smith, Kristiana S.; Sarosiek, Kristopher; Rohde, Kyle H.; Kim, Kyu Kwang; Lee, Kyung Hyeon; Pusztai, Lajos; Lehtio, Lari; Haupt, Larisa M.; Cowen, Leah E.; Byrne, Lee J.; Su, Leila; Wert-Lamas, Leon; Puchades-Carrasco, Leonor; Chen, Lifeng; Malkas, Linda H.; Zhuo, Ling; , ; Hedstrom, Lizbeth; Walensky, Loren D.; Antonelli, Lorenzo; Iommarini, Luisa; Whitesell, Luke; Randall, Lia M.; Fathallah, M. Dahmani; Nagai, Maira Harume; Kilkenny, Mairi Louise; Ben-Johny, Manu; Lussier, Marc P.; Windisch, Marc P.; Lolicato, Marco; Lolli, Marco Lucio; Vleminckx, Margot; Caroleo, Maria Cristina; Macias, Maria J.; Valli, Marilia; Barghash, Marim M.; Mellado, Mario; Tye, Mark A.; Wilson, Mark A.; Hannink, Mark; Ashton, Mark R.; Cerna, Mark Vincent C.dela; Giorgis, Marta; Safo, Martin K.; Maurice, Martin St; McDowell, Mary Ann; Pasquali, Marzia; Mehedi, Masfique; Serafim, Mateus Sá Magalhães; Soellner, Matthew B.; Alteen, Matthew G.; Champion, Matthew M.; Skorodinsky, Maxim; O"™Mara, Megan L.; Bedi, Mel; Rizzi, Menico; Levin, Michael; Mowat, Michael; Jackson, Michael R.; Paige, Mikell; Al-Yozbaki, Minnatallah; Giardini, Miriam A.; Maksimainen, Mirko M.; De Luise, Monica; Hussain, Muhammad Saddam; Christodoulides, Myron; Stec, Natalia; Zelinskaya, Natalia; Van Pelt, Natascha; Merrill, Nathan M.; Singh, Nathanael; Kootstra, Neeltje A.; Singh, Neeraj; Gandhi, Neha S.; Chan, Nei Li; Trinh, Nguyen Mai; Schneider, Nicholas O.; Matovic, Nick; Horstmann, Nicola; Longo, Nicola; Bharambe, Nikhil; Rouzbeh, Nirvan; Mahmoodi, Niusha; Gumede, Njabulo Joyfull; Anastasio, Noelle C.; Khalaf, Noureddine Ben; Rabal, Obdulia; Kandror, Olga; Escaffre, Olivier; Silvennoinen, Olli; Bishop, Ozlem Tastan; Iglesias, Pablo; Sobrado, Pablo; Chuong, Patrick; O"™Connell, Patrick; Martin-Malpartida, Pau; Mellor, Paul; Fish, Paul V.; Moreira, Paulo Otávio Lourenço; Zhou, Pei; , ; Liu, Pengda; Wu, Pengpeng; Agogo-Mawuli, Percy; Jones, Peter L.; Ngoi, Peter; Toogood, Peter; Ip, Philbert; von Hundelshausen, Philipp; Lee, Pil H.; Rowswell-Turner, Rachael B.; Balaña-Fouce, Rafael; Rocha, Rafael Eduardo Oliveira; Guido, Rafael V.C.; Ferreira, Rafaela Salgado; Agrawal, Rajendra K.; Harijan, Rajesh K.; Ramachandran, Rajesh; Verma, Rajkumar; Singh, Rakesh K.; Tiwari, Rakesh Kumar; Mazitschek, Ralph; Koppisetti, Rama K.; Dame, Remus T.; Douville, Renée N.; Austin, Richard C.; Taylor, Richard E.; Moore, Richard G.; Ebright, Richard H.; Angell, Richard M.; Yan, Riqiang; Kejriwal, Rishabh; Batey, Robert A.; Blelloch, Robert; Vandenberg, Robert J.; Hickey, Robert J.; Kelm, Robert J.; Lake, Robert J.; Bradley, Robert K.; Blumenthal, Robert M.; Solano, Roberto; Gierse, Robin Matthias; Viola, Ronald E.; McCarthy, Ronan R.; Reguera, Rosa Maria; Uribe, Ruben Vazquez; do Monte-Neto, Rubens Lima; Gorgoglione, Ruggiero; Cullinane, Ryan T.; Katyal, Sachin; Hossain, Sakib; Phadke, Sameer; Shelburne, Samuel A.; Geden, Sandra E.; Johannsen, Sandra; Wazir, Sarah; Legare, Scott; Landfear, Scott M.; Radhakrishnan, Senthil K.; Ammendola, Serena; Dzhumaev, Sergei; Seo, Seung Yong; Li, Shan; Zhou, Shan; Chu, Shaoyou; Chauhan, Shefali; Maruta, Shinsaku; Ashkar, Shireen R.; Shyng, Show Ling; Conticello, Silvestro G.; Buroni, Silvia; Garavaglia, Silvia; White, Simon J.; Zhu, Siran; Tsimbalyuk, Sofiya; Chadni, Somaia Haque; Byun, Soo Young; Park, Soonju; Xu, Sophia Q.; Banerjee, Sourav; Zahler, Stefan; Espinoza, Stefano; Gustincich, Stefano; Sainas, Stefano; Celano, Stephanie L.; Capuzzi, Stephen J.; Waggoner, Stephen N.; Poirier, Steve; Olson, Steven H.; Marx, Steven O.; Van Doren, Steven R.; Sarilla, Suryakala; Brady-Kalnay, Susann M.; Dallman, Sydney; Azeem, Syeda Maryam; Teramoto, Tadahisa; Mehlman, Tamar; Swart, Tarryn; Abaffy, Tatjana; Akopian, Tatos; Haikarainen, Teemu; Moreda, Teresa Lozano; Ikegami, Tetsuro; Teixeira, Thaiz Rodrigues; Jayasinghe, Thilina D.; Gillingwater, Thomas H.; Kampourakis, Thomas; Richardson, Timothy I.; Herdendorf, Timothy J.; Kotzé, Timothy J.; O"™Meara, Timothy R.; Corson, Timothy W.; Hermle, Tobias; Ogunwa, Tomisin Happy; Lan, Tong; Su, Tong; Banjo, Toshihiro; O"™Mara, Tracy A.; Chou, Tristan; Chou, Tsui Fen; Baumann, Ulrich; Desai, Umesh R.; Pai, Vaibhav P.; Thai, Van Chi; Tandon, Vasudha; Banerji, Versha; Robinson, Victoria L.; Gunasekharan, Vignesh; Namasivayam, Vigneshwaran; Segers, Vincent F.M.; Maranda, Vincent; Dolce, Vincenza; Maltarollo, Vinicius Gonçalves; Scoffone, Viola Camilla; Woods, Virgil A.; Ronchi, Virginia Paola; Van Hung Le, Vuong; Clayton, W. Brent; Lowther, W. Todd; Houry, Walid A.; Li, Wei; Tang, Weiping; Zhang, Wenjun; Van Voorhis, Wesley C.; Donaldson, William A.; Hahn, William C.; Kerr, William G.; Gerwick, William H.; Bradshaw, William J.; Foong, Wuen Ee; Blanchet, Xavier; Wu, Xiaoyang; Lu, Xin; Qi, Xin; Xu, Xin; Yu, Xinfang; Qin, Xingping; Wang, Xingyou; Yuan, Xinrui; Zhang, Xu; Zhang, Yan Jessie; Hu, Yanmei; Aldhamen, Yasser Ali; Chen, Yicheng; Li, Yihe; Sun, Ying; Zhu, Yini; Gupta, Yogesh K.; Pérez-Pertejo, Yolanda; Li, Yong; Tang, Young; He, Yuan; Tse-Dinh, Yuk Ching; Sidorova, Yulia A.; Yen, Yun; Li, Yunlong; Frangos, Zachary J.; Chung, Zara; Su, Zhengchen; Wang, Zhenghe; Zhang, Zhiguo; Liu, Zhongle; Inde, Zintis; Artia, Zoraima; Heifets, Abraham
High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery.
SCOPUS:85191821387
ISSN: 2045-2322
CID: 5658952
Correction to: AI is a viable alternative to high throughput screening: a 318-target study (Scientific Reports, (2024), 14, 1, (7526), 10.1038/s41598-024-54655-z)
Giles, Ellie; Heifets, Abraham; Artia, Zoraima; Inde, Zintis; Liu, Zhongle; Zhang, Zhiguo; Wang, Zhenghe; Su, Zhengchen; Chung, Zara; Frangos, Zachary J.; Li, Yunlong; Yen, Yun; Sidorova, Yulia A.; Tse-Dinh, Yuk Ching; He, Yuan; Tang, Young; Li, Yong; Pérez-Pertejo, Yolanda; Gupta, Yogesh K.; Zhu, Yini; Sun, Ying; Li, Yihe; Chen, Yicheng; Aldhamen, Yasser Ali; Hu, Yanmei; Zhang, Yan Jessie; Zhang, Xu; Yuan, Xinrui; Wang, Xingyou; Qin, Xingping; Yu, Xinfang; Xu, Xin; Qi, Xin; Lu, Xin; Wu, Xiaoyang; Blanchet, Xavier; Foong, Wuen Ee; Bradshaw, William J.; Gerwick, William H.; Kerr, William G.; Hahn, William C.; Donaldson, William A.; Van Voorhis, Wesley C.; Zhang, Wenjun; Tang, Weiping; Li, Wei; Houry, Walid A.; Lowther, W. Todd; Clayton, W. Brent; Van Hung Le, Vuong; Ronchi, Virginia Paola; Woods, Virgil A.; Scoffone, Viola Camilla; Maltarollo, Vinicius Gonçalves; Dolce, Vincenza; Maranda, Vincent; Segers, Vincent F.M.; Namasivayam, Vigneshwaran; Gunasekharan, Vignesh; Robinson, Victoria L.; Banerji, Versha; Tandon, Vasudha; Thai, Van Chi; Pai, Vaibhav P.; Desai, Umesh R.; Baumann, Ulrich; Chou, Tsui Fen; Chou, Tristan; O"™Mara, Tracy A.; Banjo, Toshihiro; Su, Tong; Lan, Tong; Ogunwa, Tomisin Happy; Hermle, Tobias; Corson, Timothy W.; O"™Meara, Timothy R.; Kotzé, Timothy J.; Herdendorf, Timothy J.; Richardson, Timothy I.; Kampourakis, Thomas; Gillingwater, Thomas H.; Jayasinghe, Thilina D.; Teixeira, Thaiz Rodrigues; Ikegami, Tetsuro; Moreda, Teresa Lozano; Haikarainen, Teemu; Akopian, Tatos; Abaffy, Tatjana; Swart, Tarryn; Mehlman, Tamar; Teramoto, Tadahisa; Azeem, Syeda Maryam; Dallman, Sydney; Brady-Kalnay, Susann M.; Sarilla, Suryakala; Van Doren, Steven R.; Marx, Steven O.; Olson, Steven H.; Poirier, Steve; Waggoner, Stephen N.; Capuzzi, Stephen J.; Celano, Stephanie L.; Sainas, Stefano; Gustincich, Stefano; Espinoza, Stefano; Zahler, Stefan; Banerjee, Sourav; Xu, Sophia Q.; Park, Soonju; Byun, Soo Young; Chadni, Somaia Haque; Tsimbalyuk, Sofiya; Zhu, Siran; White, Simon J.; Garavaglia, Silvia; Buroni, Silvia; Conticello, Silvestro G.; Shyng, Show Ling; Ashkar, Shireen R.; Maruta, Shinsaku; Chauhan, Shefali; Chu, Shaoyou; Zhou, Shan; Li, Shan; Seo, Seung Yong; Dzhumaev, Sergei; Ammendola, Serena; Radhakrishnan, Senthil K.; Landfear, Scott M.; Legare, Scott; Wazir, Sarah; Johannsen, Sandra; Geden, Sandra E.; Shelburne, Samuel A.; Phadke, Sameer; Hossain, Sakib; Katyal, Sachin; Cullinane, Ryan T.; Gorgoglione, Ruggiero; do Monte-Neto, Rubens Lima; Uribe, Ruben Vazquez; Reguera, Rosa Maria; McCarthy, Ronan R.; Viola, Ronald E.; Gierse, Robin Matthias; Solano, Roberto; Blumenthal, Robert M.; Bradley, Robert K.; Lake, Robert J.; Kelm, Robert J.; Hickey, Robert J.; Vandenberg, Robert J.; Blelloch, Robert; Batey, Robert A.; Kejriwal, Rishabh; Yan, Riqiang; Angell, Richard M.; Ebright, Richard H.; Moore, Richard G.; Taylor, Richard E.; Austin, Richard C.; Douville, Renée N.; Dame, Remus T.; Koppisetti, Rama K.; Mazitschek, Ralph; Tiwari, Rakesh Kumar; Singh, Rakesh K.; Verma, Rajkumar; Ramachandran, Rajesh; Harijan, Rajesh K.; Agrawal, Rajendra K.; Ferreira, Rafaela Salgado; Guido, Rafael V.C.; Rocha, Rafael Eduardo Oliveira; Balaña-Fouce, Rafael; Rowswell-Turner, Rachael B.; Lee, Pil H.; von Hundelshausen, Philipp; Ip, Philbert; Toogood, Peter; Ngoi, Peter; Jones, Peter L.; Agogo-Mawuli, Percy; Wu, Pengpeng; Liu, Pengda; Zhou, Pei; Moreira, Paulo Otávio Lourenço; Fish, Paul V.; Mellor, Paul; Martin-Malpartida, Pau; O"™Connell, Patrick; Chuong, Patrick; Sobrado, Pablo; Iglesias, Pablo; Bishop, Ozlem Tastan; Silvennoinen, Olli; Escaffre, Olivier; Kandror, Olga; Rabal, Obdulia; Khalaf, Noureddine Ben; Anastasio, Noelle C.; Gumede, Njabulo Joyfull; Mahmoodi, Niusha; Rouzbeh, Nirvan; Bharambe, Nikhil; Longo, Nicola; Horstmann, Nicola; Matovic, Nick; Schneider, Nicholas O.; Trinh, Nguyen Mai; Chan, Nei Li; Gandhi, Neha S.; Singh, Neeraj; Kootstra, Neeltje A.; Singh, Nathanael; Merrill, Nathan M.; Van Pelt, Natascha; Zelinskaya, Natalia; Stec, Natalia; Christodoulides, Myron; Hussain, Muhammad Saddam; De Luise, Monica; Maksimainen, Mirko M.; Giardini, Miriam A.; Al-Yozbaki, Minnatallah; Paige, Mikell; Jackson, Michael R.; Mowat, Michael; Levin, Michael; Rizzi, Menico; Bedi, Mel; O"™Mara, Megan L.; Skorodinsky, Maxim; Champion, Matthew M.; Alteen, Matthew G.; Soellner, Matthew B.; Serafim, Mateus Sá Magalhães; Mehedi, Masfique; Pasquali, Marzia; McDowell, Mary Ann; Maurice, Martin St; Safo, Martin K.; Giorgis, Marta; Cerna, Mark Vincent C.dela; Ashton, Mark R.; Hannink, Mark; Wilson, Mark A.; Tye, Mark A.; Mellado, Mario; Barghash, Marim M.; Valli, Marilia; Macias, Maria J.; Caroleo, Maria Cristina; Vleminckx, Margot; Lolli, Marco Lucio; Lolicato, Marco; Windisch, Marc P.; Lussier, Marc P.; Ben-Johny, Manu; Kilkenny, Mairi Louise; Nagai, Maira Harume; Fathallah, M. Dahmani; Randall, Lia M.; Whitesell, Luke; Iommarini, Luisa; Antonelli, Lorenzo; Walensky, Loren D.; Hedstrom, Lizbeth; Zhuo, Ling; Malkas, Linda H.; Chen, Lifeng; Puchades-Carrasco, Leonor; Wert-Lamas, Leon; Su, Leila; Byrne, Lee J.; Cowen, Leah E.; Haupt, Larisa M.; Lehtio, Lari; Pusztai, Lajos; Lee, Kyung Hyeon; Kim, Kyu Kwang; Rohde, Kyle H.; Sarosiek, Kristopher; Smith, Kristiana S.; Liu, Koting; Korotkov, Konstantin V.; Mostert, Konrad J.; Nagamori, Kiyo; Faller, Kiterie M.E.; Musta, Kirsikka; McManus, Kirk James; Sugamori, Kim S.; Ghilarducci, Kim; Pham, Kien; Machaca, Khaled; Parang, Keykavous; Hopkins, Kevin M.; Lobb, Kevin A.; Lai, Kent; Wentworth, Kelly L.; Wong, Keith S.; Ojo, Kayode K.; Gadar, Kavita; Martin, Katie R.; Cunningham, Kathryn A.; Molyneaux, Kathleen A.; Hansen, Kasper B.; Francisco, Karol R.; Sishtla, Kamakshi; Abrahão, Jônatas Santos; Sistla, Jyothi C.; Liao, Junzhuo; Kee, Jung Min; Wang, Jun; Bogomolovas, Julijus; Lescar, Julien; Cools, Julie; Milosavljevic, Julian; Oyarzabal, Julen; Lasarte, Juan José; Arias, Juan Antonio Sanchez; Rodriguez-Frade, José Miguel; Watkins, Joshua; Finkelstein, Joshua M.; Gruber, Joshua J.; Nasburg, Joshua Alexander; Maciag, Joseph J.; Rayman, Joseph B.; Costoya, Jose A.; Pederick, Jordan L.; So, Jonathan; Pascal, John M.; Tanner, John J.; Coles, John G.; Bruning, John Burt; Bruning, John B.; Stetefeld, Joerg; Reis, Joana; Lee, Jiyoun; Lin, Jiusheng; Zhao, Jinshi; Xu, Jingyi; Liao, Jiayu; Zhu, Jiaqi; Wang, Jianghai; Xu, Jiake; Lin, Jiabei; Zhou, Jia; Jossart, Jennifer N.; MacKeigan, Jeffrey P.; Dickhout, Jeffrey; Evans, Jay D.; Maynes, Jason T.; Mousa, Jarrod J.; Chuah, Janelle; Gebauer, Jan M.; Voss, Jan Hendrik; Shorter, James; Ng, James; Granneman, James G.; Siqueira-Neto, Jair L.; Miner, Jaden; Kratz, Jadel Müller; Fries, Jacob; Ferreira, Jacob; Boorman, Jacob; Kwiatkowski, Jacek; Perry, J. Jefferson P.; Cakir, Isin; Lotsaris, Irina; Qureshi, Insaf Ahmed; Verhamme, Ingrid M.; Mungrue, Imran N.; Arozarena, Imanol; Corvo, Ileana; Caliandro, Ileana; Greig, Iain R.; Kim, Hyeong Jun; Zhou, Hui; Feng, Hui; Fan, Hua Ying; Jung, Hoyoung; Lieberman, Howard B.; Debonsi, Hosana Maria; Xu, Hongyang; Van Remmen, Holly; Tam, Heng Keat; Chaytow, Helena; Hoppe, Heinrich; Wulff, Heike; Shim, Heesung; Yuan, Haynes; Tilford, Hannah; Moore, Hannah P.; Zhou, Han; Jafar-Nejad, Hamed; Breton, Hairol E.; Li, Hai; Cildir, Gokhan; Lee, Gyeongeun; Rucinski, Gwennan; Alvarez, Guzmán; Caljon, Guy; Akk, Gustav; de Souza, Guilherme Eduardo; Veit, Guido; Popowicz, Grzegorz Maria; Bowman, Gregory R.; Stuchbury, Grant David; Conn, Graeme L.; Michlewski, Gracjan; Dahal, Gopal; Leuzzi, Giuseppe; Gasparre, Giuseppe; Fiermonte, Giuseppe; Girolimetti, Giulia; Roti, Giovanni; Cortopassi, Gino; De Keulenaer, Gilles; Colotti, Gianni; Parico, Gian Carlo G.; Prikler, Gergely; Lukacs, Gergely L.; Garcia, George A.; Greene, Geoffrey L.; Mayer, Gaétan; Eitzen, Gary; Dempsey, Garrett; Zhang, Gang; Lembo, Gaia; Bognár, Gabriella; Rodriguez, G. Marcela; Svensson, Fredrik; Bdira, Fredj Ben; Vizeacoumar, Frederick S.; Buckner, Frederick S.; Luh, Frank; Vizeacoumar, Franco J.; Borriello, Francesco; van den Akker, Focco; Ingoglia, Filippo; Wang, Feng; Leng, Fenfei; Xiang, Fei; Yu, Fang; Gavathiotis, Evripidis; Glukhov, Evgenia; Garcia-Cuesta, Eva M.; Jo, Eunji; Kroon, Erna Geessien; Fan, Erkang; Lisabeth, Erika Mathes; Cione, Erika; Thompson, Erik W.; Strauss, Erick; Rubin, Eric J.; Trakhtenberg, Ephraim F.; Petretto, Enrico; Mason, Emily R.; Christensen, Emily M.; Leung, Elisa; Mameli, Eleonora; Lama, Eleonora; Abraham, Elena Theres; Lenci, Elena; Aguilera, Elena; Silva, Elany Barbosa; Lynn, Edward G.; Hsiao, Edward C.; Gelardi, Edoardo Luigi Maria; Glubb, Dylan M.; Duncan, Dustin; Krishnamurthy, Durga; Zochodne, Douglas William; Shoue, Douglas A.; Dirksen, Dorian; Lee, Donghan; Ronning, Donald R.; Slotboom, Dirk J.; Chaudhuri, Dipayan; Zhang, Dingqiang; Alramadhani, Dina; Ortiz, Diana; Hu, Di; Welsbie, Derek S.; Coombe, Deirdre R.; Anderson, Deborah H.; Ferraris, Davide Maria; Riches, David W.H.; Krist, David T.; Shum, David; Siderovski, David P.; Moreira, David; Smith, David M.; Hosfield, David J.; Dowling, David J.; Drewry, David H.; Hildeman, David A.; Trader, Darci J.; Manor, Danny; Chen, Daniel; Lawrence, Daniel A.; Keedy, Daniel A.; Tumes, Damon J.; Luo, Dahai; Santiago, César; Paulino, Cristina; Arrigoni, Cristina; Myhr, Courtney; Wilson, Cornelia M.; Loy, Cody A.; Reglero, Clara; Alkan, Cigdem; Morisseau, Christophe; Muli, Christine S.; Zeina, Christina M.; Weber, Christian; Müller, Christa E.; Kemet, Chinyere Maat; Mantri, Chinmay Kumar; Peltier, Cheryl; Liu, Chen; Huimei, Chen; Dieck, Chelsea L.; Keller, Charles; Karan, Charles; Kahler, Charlene M.; Yang, Chao Yie; Huang, Chang; Chaton, Catherine T.; Partch, Carrie L.; Chapman, Carly J.; Bon, Carlotta; Ballatore, Carlo; Torner, Carles; Novina, Carl D.; Lempicki, Camille; Fraser, Cameron; Dickinson, Bryan C.; Mota, Bruno Eduardo Fernandes; Hammock, Bruce D.; Morten, Brianna C.; Dymock, Brian W.; Geisbrecht, Brian V.; Duggan, Brendan M.; Salas, Brenda P.Medellin; Pressly, Brandon; Agianian, Bogos; Gong, Bin; Balakrishnan, Bijina; Englinger, Bernhard; Kováts, Benjámin; Chua, Benjamin Soon Kai; Perry, Benjamin; Liou, Benjamin; Edelman, Benjamin L.; Bailey-Elkin, Ben A.; Ribeiro, Beatriz Murta Rezende Moraes; Diallo, Bakary N"™tji; O"™Dea, Austin; Colomba, Audrey; Apfel, Athena Marie; ElSheikh, Assmaa; Prince, Ashutosh; John, Ashley L.St; Paparella, Ashleigh S.; Haas, Arthur L.; Chatterjee, Arnab K.; Samantha, Ariela; Panganiban, Antonito T.; Pineda-Lucena, Antonio; Garmendia, Antonio E.; Del Rio Flores, Antonio; O"™Donoghue, Anthony J.; Virtanen, Anniina; Fiorillo, Annarita; Müller, Anna; Montanaro, Anna; Minakova, Anna; Porcelli, Anna Maria; Hirsch, Anna K.H.; D"™Antuono, Anna; Borowska, Anna; Motyl, Anna A.L.; Cathcart, Ann M.; Ojha, Anil K.; Taglialatela, Angelo; White, Andrew; Cuddihy, Andrew R.; Lam, Andrew; Reidenbach, Andrew G.; Freywald, Andrew; Berti, Andrew; Herr, Andrew B.; Stahl, Andreas; Trabocchi, Andrea; Foote, Andrea Talbot; Mattevi, Andrea; Ilari, Andrea; Chini, Andrea; Caporali, Andrea; Battistoni, Andrea; Matheeussen, An; Rangarajan, Amith Vikram; Patel, Amit K.; Caflisch, Amedeo; Bryant-Friedrich, Amanda; Garaeva, Alisa A.; Vrielink, Alice; Tomilov, Alexey; Degterev, Alexei; Gingras, Alexandre R.; Statsyuk, Alexander V.; Freiberg, Alexander N.; Kushnir, Alexander; Agoulnik, Alexander I.; de Sousa, Alessandra Mara; Sverzhinsky, Aleksandr; de Oliveira, Aldo Sena; Ciccia, Alberto; Smrcka, Alan V.; Toh, Alan Kie Leong; Shaqra, Ala M.; Mushtaq, Aisha; Ayachi, Aicha Gharbi; Ghosh, Agnidipta; Andricopulo, Adriano D.; Ferrando, Adolfo A.; Presser, Adam G.; Mysore, Venkatesh; Gupta, Tushita; Abramyan, Tigran M.; Schroedl, Stefan; Pemberton, Ryan P.; DeHaan, Nicholas; Young, Matthew A.; Goldenberg, Joshua M.; Sorenson, Jon M.; Warrington, Jeffrey M.; Cox, Bryan D.; Anderson, Brandon M.; Bergman, Bastiaan; Cann, Andrew B.; Lee, Andreia H.; Kenyon, Victor; Chern, Ting Rong; Williams, Tiffany; Van Grack, Tessa; O"™Brien, Terrence E.; Palazzo, Teresa; Hare, Stephanie; Contreras, Stephanie; Shek, Stefani; PrasadPrasad, Srimukh Veccham Krishna; Suterwala, Shabbir; de Oliveira, Saulo; Eckert, Sam; Gniewek, Pawel; Henriksen, Niel; Anthis, Nicholas J.; Ahmed, Mostafa; Mysinger, Michael; Ngo, Lien; Giesler, Kyle; Sarangapani, Krishna; Stafford, Kate; Ng, Ho Leung; van den Bedem, Henry; Truong, Ha; Friedland, Greg; Moharreri, Ehsan; Thayer, Desiree; Laggner, Christian; Butler, Brittany; Worley, Brad; Thomas, Bill; Samudio, Ben; Davtyan, Aram; O"™Sullivan, Ann Marie; Rosnik, Andreana; Stecula, Adrian; Morrison, Adrian; Ho, Gregory; Nguyen, Kong; Bernard, Denzil; Wallach, Izhar
Correction to: Scientific Reportshttps://doi.org/10.1038/s41598-024-54655-z, published online 02 April 2024 The original version of this Article contained errors. In the original version of this article, Ellie Giles was omitted from the Author list. Additionally, the following Affiliation information has been updated: 1. Affiliation 25 was incorrect. Affiliation 25 "˜Queensland University of Technology, Brisbane, USA."™ now reads, "˜Queensland University of Technology, Brisbane, Australia."™ 2. Marta Giorgis was incorrectly affiliated with the "˜University of Aberdeen, Aberdeen, UK."™ The correct Affiliation is listed below: "˜University of Turin, Turin, Italy."™ 3. Affiliations 52, 125 and 261 were duplicated. As a result, the correct Affiliation for Andrew B. Herr, Benjamin Liou, David A. Hildeman, Joseph J. Maciag, Ying Sun, Durga Krishnamurthy, and Stephen N. Waggoner is: "˜Cincinnati Children"™s Hospital Medical Center, Cincinnati, USA."™ Furthermore, an outdated version of Figure 1 was typeset. The original Figure 1 and accompanying legend appear below. (Figure presented.) Pairs of representative compounds extracted from AI patents (right) and corresponding prior patents (left) for clinical-stage programs (CDK792,93, A2Ar-antagonist94,95, MALT196,97, QPCTL98,99, USP1100,101, and 3CLpro102,103). The identical atoms between the chemical structures are highlighted in red. Lastly, The Acknowledgements section contained an error. "See Supplementary section S1." now reads, "See Supplementary section S2." The original Article has been corrected.
SCOPUS:85204723078
ISSN: 2045-2322
CID: 5714322
Personalized Ablation Strategies Optimize First Pass Isolation and Minimize Pulmonary Vein Reconnection During Paroxysmal Atrial Fibrillation Ablation
Junarta, Joey; Qiu, Jessica; Cheng, Austin V; Barbhaiya, Chirag R; Jankelson, Lior; Holmes, Douglas; Kushnir, Alexander; Knotts, Robert J; Yang, Felix; Bernstein, Scott A; Park, David S; Chinitz, Larry A; Aizer, Anthony
PMID: 39447812
ISSN: 1556-3871
CID: 5740132
Catheter ablation compared to medical therapy for ventricular tachycardia in sarcoidosis: nationwide outcomes and hospital readmissions
Gurin, Michael I; Xia, Yuhe; Tarabanis, Constantine; Goldberg, Randal I; Knotts, Robert J; Donnino, Robert; Reyentovich, Alex; Bernstein, Scott; Jankelson, Lior; Kushnir, Alexander; Holmes, Douglas; Spinelli, Michael; Park, David S; Barbhaiya, Chirag R; Chinitz, Larry A; Aizer, Anthony
BACKGROUND/UNASSIGNED:Catheter ablation (CA) for ventricular tachycardia (VT) can be a useful treatment strategy, however, few studies have compared CA to medical therapy (MT) in the sarcoidosis population. OBJECTIVE/UNASSIGNED:To assess in-hospital outcomes and unplanned readmissions following CA for VT compared to MT in patients with sarcoidosis. METHODS/UNASSIGNED:Data was obtained from the Nationwide Readmissions Database between 2010 and 2019 to identify patients with sarcoidosis admitted for VT either undergoing CA or MT during elective and non-elective admission. Primary endpoints were a composite endpoint of inpatient mortality, cardiogenic shock, cardiac arrest and 30-day hospital readmissions. Procedural complications at index admission and causes of readmission were also identified. RESULTS/UNASSIGNED: = 0.343). The most common cause of readmission were ventricular arrhythmias (VA) in both groups, however, those undergoing elective CA were less likely to be readmitted for VA compared to non-elective CA. The most common complication in the CA group was cardiac tamponade (4.8 %). CONCLUSION/UNASSIGNED:VT ablation is associated with similar rates of 30-day readmission compared to MT and does not confer increased risk of harm with respect to inpatient mortality, cardiogenic shock or cardiac arrest. Further research is warranted to determine if a subgroup of sarcoidosis patients admitted with VT are better served with an initial conservative management strategy followed by VT ablation.
PMCID:11279686
PMID: 39070127
ISSN: 2666-6022
CID: 5731242
