Publication Information

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366, 386], 'some': [285], 'therapies': [287, 1787], 'impacted': [289], 'by': [290, 717, 720, 910, 927, 945, 961, 1176], 'cardiovascular': [291, 310, 448, 1432, 1793, 2016], 'events': [292, 2017], 'ranging': [293], 'from': [294, 1027, 1315, 1524], '6%': [295], '20%': [297], 'in': [298, 349, 410, 445, 454, 466, 478, 510, 521, 547, 573, 647, 665, 674, 680, 705, 723, 745, 767, 794, 815, 862, 948, 973, 989, 1016, 1057, 1066, 1078, 1098, 1123, 1153, 1163, 1178, 1196, 1229, 1288, 1309, 1338, 1385, 1405, 1416, 1460, 1472, 1482, 1540, 1632, 1670, 1754, 1850, 1894, 1902, 1933, 1981, 2090], 'clinical': [299, 303, 446, 460, 832], 'trials.1–4': [300], 'cardio-oncological': [302], 'approach': [304], 'recognition': [307], 'specific': [309, 563, 714], 'phenotypes,': [311], 'coupled': [312], 'with': [313, 326, 367, 391, 473, 515, 651, 698, 753, 792, 818, 821, 834, 921, 1076, 1192, 1249, 1291, 1340, 1409, 1435, 1672, 1716, 1757, 1935], 'mechanistic': [314, 777, 1330], 'studies,': [315, 726, 924], 'may': [316, 550, 1038], 'not': [317, 790, 1241, 1326, 1544], 'only': [318, 1242], 'lead': [319, 551, 876, 939, 997], 'next-generation': [324], 'molecules': [325], 'onco-specificity': [328], 'but': [329, 583, 1254], 'also': [330, 519, 758, 931, 1096, 1255, 1279, 1375], 'unveil': [331], 'fundamental': [332, 1488], 'cardiac': [333, 666, 747, 1245, 1300, 1352, 1391, 1489], 'mechanisms.5Ibrutinib,': [335], 'first': [337], 'irreversible': [338], 'BTK': [339, 399, 438, 689, 704, 1891], '(Bruton': [340], 'tyrosine': [341, 959], 'kinase)': [342, 1191], 'inhibitor,': [343], 'been': [345, 388, 431, 488, 571, 901], 'tremendous': [347], 'advance': [348, 1228], 'various': [353, 568], 'lymphoid': [354, 1179, 1636], 'malignancies': [355, 1896], 'including': [356, 865], 'mantle': [357], 'cell': [358], 'lymphoma': [359], 'chronic': [361, 1635, 1674, 1717, 1813, 1852, 1936], 'lymphocytic': [362, 1675, 1718, 1814, 1853, 1937], 'leukemia,': [363], 'improving': [364], 'patient': [365], 'fairly': [369], 'well-tolerated': [370], 'therapeutic': [371], 'option': [372], 'that': [373, 462, 611, 683, 765, 1046, 1091, 1425, 1447], 'can': [374, 407, 1486, 1791], 'be': [375, 408, 827, 904, 1039], 'continued': [376], 'indefinitely': [377], 'until': [378], 'disease': [379], 'progression': [380], 'or': [381, 502, 1354, 1550], 'intolerable': [382, 417], 'toxicity.6': [383], 'Similar': [384], 'oncological': [385], 'have': [387, 430, 570, 1044, 1128], 'then': [389], 'reported': [390, 638, 1129], 'newer,': [392], 'more': [393, 1449], 'specific,': [394], 'arguably': [396], 'acalabrutinib2,7': [403], 'zanubrutinib,8': [405], 'which': [406, 1149, 1396], 'used': [409, 709], 'patients': [411, 479, 514, 549, 816, 1339, 1407, 1671, 1715, 1756, 1934, 1982], 'who': [412, 1939], 'discontinue': [413], 'ibrutinib': [414, 451, 459, 486, 612, 673, 718, 783, 1177, 1253, 1276, 1436, 2019], 'because': [415, 517, 535, 1000], 'adverse': [418, 1301], 'events.9': [419], 'In': [420, 592, 658], 'addition,': [421], 'second-generation': [422], 'compounds,': [423], 'MK-1026': [426], '(ARQ531)': [427], 'Loxo-305,': [429], 'developed': [432], 'overcome': [434], 'resistance': [435], 'first-generation': [437, 1461], 'inhibitors': [439, 820], 'currently': [442], 'being': [443, 1383], 'evaluated': [444, 669], 'trials.6,8Relevant': [447], 'risks': [449], 'therapy': [452, 1485, 1713, 1811], 'emerged': [453], 'analysis': [456, 711], 'large': [458, 800], 'trials': [461], 'indicated': [463], 'increase': [465, 492, 1282], 'incidence': [468, 812, 1335], 'atrial': [470, 640, 643, 678, 751, 887, 1021, 1079, 1084, 1164, 1200, 1979, 2049, 2091, 2098], 'fibrillation': [471, 679, 1980, 2050], '(AF),': [472], 'particularly': [475], 'increased': [476, 522, 554, 639, 811, 870, 1035, 1092, 1402], 'risk': [477, 494, 523, 555, 615, 1974], 'having': [480], 'previous': [481, 1126, 1342], 'history': [482, 1343], 'AF.1,3,10': [484], 'Moreover,': [485, 1322], 'shown': [489, 902, 1045, 1280, 1398], 'significantly': [491], 'ventricular': [496, 655, 755, 1370, 1373, 1386], 'arrhythmias,': [497], 'well': [499, 1030, 1139], 'incident': [501, 2015], 'worsening': [503], 'hypertension.11': [504], 'poses': [506], 'unique': [508], 'challenge': [509], 'management': [512, 533, 540, 564, 1977], 'AF': [516, 539, 614, 636, 695, 787, 814, 857, 999, 1058, 1154, 1236, 1337], 'it': [518], 'results': [520], 'clinically': [525], 'relevant': [526], 'bleeding': [527], 'events.': [528, 1302], 'This': [529, 1463], 'represents': [530], 'major': [532, 854, 1227], 'conundrum,': [534], 'applying': [536], 'current': [538], 'guidelines': [541], 'for': [542, 893, 1714, 1812], 'protecting': [543], 'against': [544], 'embolic': [545], 'stroke': [546], 'catastrophic': [558], 'bleed,': [559], 'necessitating': [560], 'guidelines.Multiple': [565], 'studies': [566, 1043, 1127, 1412], 'evaluating': [567], 'kinases': [569, 715], 'performed': [572], 'effort': [575, 660], 'elucidate': [577], 'mechanism': [579, 1271, 1297], 'ibrutinib-induced': [581, 635, 732, 1273], 'AF,': [582], 'they': [584, 668], 'were': [585], 'unable': [586], 'definitely': [588], 'validate': [589], 'target.': [591, 734], 'this': [593, 1323, 1541], 'issue': [594], 'Circulation,': [596], 'Xiao': [597, 928, 2026], 'et': [598, 929, 1625, 1666, 1706, 1748, 1846, 1883, 1929, 1970, 2011, 2046, 2083, 2123], 'al12': [599], 'elegantly': [600], 'chronicle': [601], 'their': [602], 'discovery': [603, 1444], 'process': [604, 899], 'unintended': [606], 'targets': [607, 664], 'ibrutinib,': [609, 1292], 'showing': [610], 'increases': [613], 'via': [616], 'off-target': [618, 1457], 'inhibitory': [619], 'effect': [620], 'CSK': [622, 728, 737, 780, 823, 937, 951, 995, 1032, 1188, 1266, 1310], '(C-terminal': [623, 1189], 'kinase).': [625], 'Their': [626], 'study': [627, 926, 1464, 1887], 'established': [628, 727], 'characterized': [630], 'murine': [632, 796], 'model': [633], 'refractory': [641], 'periods,': [642], 'fibrosis,': [644], 'dilation': [646], 'inflammatory': [649, 743, 1036, 1257, 1422], 'milieu,': [650], 'preserved': [653, 754], 'left': [654, 750], 'ejection': [656], 'fraction.': [657], 'identify': [662], 'ibrutinib-specific': [663], 'myocytes,': [667], 'impact': [671], 'induction': [676], 'BTKxid': [681], 'mice': [682, 739, 769, 1289, 1312], 'harbor': [684], 'mutant': [686], 'nonfunctional': [688], 'demonstrated': [691, 759], 'persistence': [692], 'phenotype': [696, 1022], 'consistent': [697], 'lack': [700, 1367], 'involvement': [702], 'its': [706], 'pathophysiology.They': [707], 'further': [708, 933, 1070, 1157, 1320], 'chemoproteomic': [710], 'evaluate': [713, 807], 'inhibited': [716], 'and,': [719], 'using': [721], 'serial': [722], 'vivo': [724], 'inhibitor': [725, 1892], 'leading': [731], 'arrhythmogenic': [733], 'Conditional,': [735], 'cardiomyocyte-specific': [736], 'knockout': [738, 1033, 1311], 'recapitulated': [740], 'similar': [742, 763, 1305], 'infiltrate': [744], 'myocytes': [748], 'enlargement,': [752], 'function.': [756], 'They': [757], 'cytokine': [761, 1258], 'profile': [762, 1360], 'seen': [766], 'ibrutinib-treated': [768, 1028, 1102, 1124], 'overlapping': [772], 'gene': [773], 'expression': [774, 1144, 2093], 'pattern': [775], 'suggesting': [776, 1294], 'similarities': [778], 'between': [779, 1108, 1131], 'loss': [781, 1002], 'use.': [784, 1437], 'Importantly,': [785, 1365], 'outcome': [788, 1306], 'was': [789, 804, 1095, 1121, 1278, 1307, 1325], 'observed': [791, 1097, 1122, 1248, 1308, 1369, 1434, 1459], 'acalabrutinib': [793], 'models.': [797], 'Furthermore,': [798, 1115], 'international,': [801], 'pharmacovigilance': [802, 1262], 'database': [803], 'queried': [805], 'confirm': [809], 'treated': [817, 1290, 1408, 1634], 'nonspecific': [822], 'targeting.AF': [824], 'continues': [825], 'most': [829], 'common': [830], 'sustained': [831], 'arrhythmia,': [833], 'complex': [836], 'incompletely': [838], 'understood': [839], 'pathophysiology.': [841], 'Focal': [842], 'ectopic': [843, 882], 'activity': [844, 1048], 'electric': [846, 1119, 1165], 'reentry': [847, 894], 'commonly': [849], 'considered': [850], '2': [853, 1679], 'determinants': [855], 'initiation': [858, 1197], 'maintenance.': [860], 'Abnormalities': [861], 'calcium': [863, 1082, 1208], 'handling,': [864], 'leaky': [866], 'sarcoplasmic': [867, 1221], 'reticulum': [868], 'NCX': [871], '(Na+/Ca2+': [872], 'transmembrane': [873], 'exchanger)': [874], 'currents,': [875], 'delayed': [878], 'after-depolarizations': [879], 'trigger': [881], 'activities.': [883], 'Electric': [884], 'structural': [886, 1246], 'remodeling': [888, 898, 1120, 1166], 'provide': [889, 1329], 'vulnerable': [891], 'substrate': [892], 'activities,': [895], 'influenced': [905], 'at': [906, 1401, 1477], 'level': [909], 'stress': [911], 'signaling': [912, 1010, 1037, 1062, 1133, 1173], 'pathways13': [914], 'CaMKII': [916, 1072, 1093, 1110], '(calmodulin-dependent': [917], 'protein': [918, 1143, 1204], 'II).14As': [920], 'great': [923, 1467], 'al': [930], 'opens': [932], 'questions.': [934], 'How': [935], 'does': [936], 'suppression': [938, 996], 'AF?': [941, 1017], 'As': [942], 'pointed': [943], 'out': [944], 'authors,': [947], 'tumor': [949, 1180], 'cells,': [950], 'suppresses': [952], 'activities': [954], 'SFKs': [956, 968], '(Src': [957], 'family': [958], 'kinases)': [960], 'phosphorylating': [962], 'residues': [963], 'C-terminal': [966, 2055], 'end.': [967], 'play': [969, 988, 1012, 1150], 'multiple': [970], 'critical': [971, 1055, 1151], 'roles': [972, 1152], 'wide': [975], 'variety': [976], 'cells': [978, 1181], 'tissues.': [980], 'However,': [981], 'our': [982], 'understanding': [983, 1231, 1440], 'role': [986, 1015, 1056], 'CSK/SFKs': [987, 1161], 'cardiomyocytes': [990, 1183], 'quite': [992], 'limited.': [993], 'Does': [994, 1007], 'inhibition': [1004, 2053], 'SFKs?': [1006], 'CSK/SFK': [1009, 1061, 1113, 1132], 'pathway': [1011, 1111, 1423], 'general': [1014], 'Based': [1018], 'RNAseq': [1024], 'data': [1025, 1263], 'obtained': [1026], 'mice,': [1034, 1125], 'culprit.': [1041], 'Previous': [1042, 2106], 'enhanced': [1047], 'NLRP3': [1051], 'inflammasome': [1052, 1064], 'plays': [1053], 'pathogenesis.15': [1059], 'Whether': [1060, 1303], 'triggers': [1063], 'activation': [1065, 1073], 'atria': [1068, 1100], 'awaits': [1069], 'investigation.Excessive': [1071], 'associated': [1075], 'changes': [1077, 2089], 'membrane': [1080], 'excitability,': [1081], 'mishandling,': [1083], 'remodeling,': [1085], 'inflammation.': [1087], 'It': [1088, 1240, 1346], 'interesting': [1090], 'phosphorylation': [1094], 'mice.': [1103], 'Is': [1104], 'there': [1105], 'interaction': [1107], 'signaling?': [1114], 'although': [1116], 'no': [1117, 1536], 'significant': [1118], 'association': [1130], 'potassium': [1135], 'channel': [1136, 2092], 'activity,': [1137], 'gap': [1141], 'junction': [1142], 'function,': [1146], 'both': [1147], 'pathogenesis.': [1155], 'Therefore,': [1156], 'characterization': [1158], 'cascade': [1162], 'warranted': [1168], '(Figure).Download': [1169], 'figureDownload': [1170], 'PowerPointFigure.': [1171], 'Molecular': [1172], 'pathways': [1174, 1382], 'engaged': [1175], 'vs': [1182], 'putative': [1185], 'connections': [1186], 'substrates': [1194], 'involved': [1195], 'maintenance': [1199], 'fibrillation.CaMKII': [1201], 'indicates': [1202], 'calcium/calmodulin-dependent': [1203], 'II;': [1206], 'ICa,': [1207], 'channels;': [1209, 1212], 'INa,': [1210], 'sodium': [1211], 'NCX,': [1213], 'sodium-calcium': [1214], 'exchanger;': [1215], 'RYR,': [1216], 'ryanodine': [1217], 'receptor;': [1218], 'SR,': [1220], 'reticulum.This': [1222], 'report': [1223, 1317, 1324], 'serves': [1224], 'pathophysiology': [1234], 'related': [1237], 'ibrutinib.': [1239, 1410], 'details': [1243], 'derangements': [1247], 'use': [1251], 'alterations': [1259], 'real-world': [1261], 'establish': [1265], 'targeting': [1267], 'valid': [1270], 'AF.': [1274, 1345], 'Interestingly,': [1275], 'systolic': [1283], 'diastolic': [1285], 'blood': [1286], 'pressures': [1287], 'hence': [1293], 'possible': [1296], 'non–AF-related': [1299], 'uncertain': [1314], 'requires': [1319], 'investigation.': [1321], 'designed': [1327], 'explanations': [1331], 'about': [1332, 1379], 'higher': [1334], 'unclear': [1348], 'whether': [1349], 'underlying': [1351], 'injury': [1353], 'predisposition': [1355], 'somehow': [1356], 'primes': [1357], 'kinome': [1359], 'promote': [1362], 'outcomes.': [1364], 'dysfunction': [1371], 'tachyarrhythmias': [1374], 'raises': [1376], 'important': [1377], 'questions': [1378], 'potential': [1380], 'alternate': [1381], 'active': [1384], 'tachycardia,': [1387], 'fibrillation,': [1388], 'sudden': [1390], 'death': [1392], 'events,': [1393], 'all': [1394], 'occur': [1400], 'frequency,': [1403], 'especially': [1404], 'older': [1406, 1755], 'Additional': [1411], 'therefore': [1414], 'essential': [1415], 'detailing': [1417], 'metabolic,': [1419], 'electric,': [1420], 'cross-talk': [1424], 'will': [1426, 1441], 'explain': [1427], 'entire': [1429], 'scope': [1430], 'toxicity': [1433], 'An': [1438], 'allow': [1442], 'rational': [1443], 'agents': [1446], 'toward': [1451], 'malignant': [1453], 'target': [1454], 'without': [1455], 'toxicities': [1458], 'compounds.': [1462], 'another': [1466], 'example': [1468], 'conceptual': [1470], 'bridges': [1471], 'cardio-oncology,': [1473], 'how': [1475, 1783], 'investigation': [1476], 'cellular': [1478], 'levels': [1481], 'reveal': [1487], 'biological': [1490], 'paradigms.DisclosuresDr': [1491], 'provided': [1494], 'consulting': [1495], 'services': [1496], 'Genentech,': [1498], 'Astrazeneca,': [1499], 'Abbvie,': [1500], 'Janssen,': [1501], 'Pharmacyclics,': [1502], 'Gilead': [1503], 'Sciences,': [1504], 'Kite': [1505], 'Pharma,': [1506, 1510], 'Celgene,': [1507], 'Karyopharm,': [1508], 'MEI': [1509], 'Verastem,': [1511], 'Incyte,': [1512], 'Beigene,': [1513], 'Johnson': [1514], 'Johnson,': [1516], 'Dava': [1518], 'Oncology.': [1519], 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