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Research & practice in thrombosis & haemostasis. 2020:Conference:(International).DOI: 10.1002/rth2.12393

Antisense oligonucleotide targeting of thrombopoietin represents a novel platelet depletion method to assess the role of platelets during inflammation resolution [Meeting Abstract]

Barrett, T; Wu, B; Revenko, A; Macleod, A R; Segal, L; Berger, J
Background: Platelets are effector cells of the innate and adaptive immune system; however, understanding their role during inflammation can be challenging due to drawbacks associated with current platelet depletion methods. The generation of antisense oligonucleotides (ASO) directed to thrombopoietin (Thpo) mRNA represents a novel method to reduce platelet count to aid in elucidating the role of platelets during inflammation.
Aim(s): To understand if Thpo-targeted ASOs represent a viable strategy to reduce platelet count in mice, and to delineate the role of platelets to inflammation resolution during lower airway dysbiosis.
Method(s): Mice were treated with a Thpo-targeted ASO and the abundance of platelets, blood cells and bone marrow hematopoietic progenitor cells assessed. Additionally, platelet responsiveness to agonists and surface expression of P-selection and JON/A was measured. To assess the contribution of platelets to inflammation resolution Thpo-ASO and control-ASO treated mice were challenged with a bacteria cocktail to model lower airway dysbiosis. Thpo-ASO mediated platelet depletion was compared to anti-CD42b platelet depletion in the lung dysbiosis model.
Result(s): ASO-mediated silencing of hepatic Thpo reduces platelet, megakaryocyte, and megakaryocyte progenitor count by 50% relative to control ASO treated mice. Thpo-ASO treatment does not alter platelet reactivity to agonists, or platelet size. Following bacterial inoculation, we found a significant increase in lung platelet-leukocyte aggregates and consistent with a response to inflammation an increase in lung Ly6Chi monocytes and macrophages in inoculated mice. Platelet depletion, by either Thpo-ASO or anti-CD42b treatment, reduces the accumulation of lung inflammatory immune cells, including monocytes (Ly6Chi) and macrophages (CD45+CD11b+F4/80+). Furthermore, we found that in contrast to anti-CD42b platelet depletion, Thpo-ASO mediated depletion allows for introduction of new platelets.
Conclusion(s): Thpo ASO-mediated platelet depletion represents a viable approach to reduce platelet count. Platelet count directly impacts lung inflammation resolution during lower airway dysbiosis demonstrating the essential role of platelets in pulmonary immune defense
EMBASE:633543730
ISSN: 2475-0379
CID: 4711242
EClinicalMedicine. 2020:24.DOI: 10.1016/j.eclinm.2020.100434

Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: A case series

Rapkiewicz, Amy V; Mai, Xingchen; Carsons, Steven E; Pittaluga, Stefania; Kleiner, David E; Berger, Jeffrey S; Thomas, Sarun; Adler, Nicole M; Charytan, David M; Gasmi, Billel; Hochman, Judith S; Reynolds, Harmony R
Background/UNASSIGNED:There is increasing recognition of a prothrombotic state in COVID-19. Post-mortem examination can provide important mechanistic insights. Methods/UNASSIGNED:We present a COVID-19 autopsy series including findings in lungs, heart, kidneys, liver, and bone, from a New York academic medical center. Findings/UNASSIGNED: = 2). Platelet-rich peri‑tubular fibrin microthrombi were a prominent renal feature. Acute tubular necrosis, and red blood cell and granular casts were seen in multiple cases. Significant glomerular pathology was notably absent. Numerous platelet-fibrin microthrombi were identified in hepatic sinusoids. All lungs exhibited diffuse alveolar damage (DAD) with a spectrum of exudative and proliferative phases including hyaline membranes, and pneumocyte hyperplasia, with viral inclusions in epithelial cells and macrophages. Three cases had superimposed acute bronchopneumonia, focally necrotizing. Interpretation/UNASSIGNED:In this series of seven COVID-19 autopsies, thrombosis was a prominent feature in multiple organs, in some cases despite full anticoagulation and regardless of timing of the disease course, suggesting that thrombosis plays a role very early in the disease process. The finding of megakaryocytes and platelet-rich thrombi in the lungs, heart and kidneys suggests a role in thrombosis. Funding/UNASSIGNED:None.
PMCID:7316051
PMID: 32766543
ISSN: 2589-5370
CID: 4555682
Circulation. Cardiovascular quality & outcomes. 2020:13(7).DOI: 10.1161/CIRCOUTCOMES.119.006399

Incidence and Factors Associated With Major Amputation in Patients With Peripheral Artery Disease: Insights From the EUCLID Trial

Long, Chandler A; Mulder, Hillary; Fowkes, F Gerry R; Baumgartner, Iris; Berger, Jeffrey S; Katona, Brian G; Mahaffey, Kenneth W; Norgren, Lars; Blomster, Juuso I; Rockhold, Frank W; Hiatt, William R; Patel, Manesh R; Jones, W Schuyler; Nehler, Mark R
BACKGROUND:Peripheral artery disease (PAD) is associated with increased risk of mortality, cardiovascular morbidity, and major amputation. Data on major amputation from a large randomized trial that included a substantial cohort of patients without critical limb ischemia (CLI) have not been described. The objective was to describe the incidence and types of amputations in the EUCLID trial (Examining Use of Ticagrelor in Peripheral Artery Disease) population, subcategorize amputations in the CLI versus no CLI cohorts, and describe the events surrounding major amputation. METHODS AND RESULTS/RESULTS:Postrandomization major amputation was analyzed in the EUCLID trial. Patients were stratified by baseline CLI status. The occurrence of major amputation was ascertained and defined as the highest level. Perioperative events surrounding major amputation were obtained including acute limb ischemia, revascularization, and all-cause mortality. All variables were assessed for significance in univariable and multivariable models. The rate of major amputation during the course of the trial was 1.6% overall, 8.4% in the CLI at baseline group, and 1.2% in the no CLI at baseline group. The annualized rate of major amputation was 0.6% in PAD overall, 3.9% in the CLI at baseline group, and 0.5% in the no CLI at baseline group. Several factors were associated with increased risk of major amputation, including history of amputation, the presence of diabetes mellitus, baseline Rutherford category 4 to 6, and an ankle-brachial index <0.8. Factors associated with a lower risk for major amputation included prior statin use. The 30-day mortality rate after major amputation was 6.5% overall, 5.6% in the CLI at baseline group, and 6.8% in the no CLI at baseline group. The annual mortality rate following major amputation was 22.8% in the CLI at baseline group and 16.0% in the no CLI at baseline group. CONCLUSIONS:The risk factors for major amputation in EUCLID patients are similar to previous large registries' reports except for diabetes mellitus in patients with CLI. The mortality following major amputation is lower in the EUCLID trial compared with registry data. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01732822.
PMID: 32615798
ISSN: 1941-7705
CID: 4537432
New England journal of medicine. 2020:382(25):2441-2448.DOI: 10.1056/NEJMoa2008975

Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Covid-19

Reynolds, Harmony R; Adhikari, Samrachana; Pulgarin, Claudia; Troxel, Andrea B; Iturrate, Eduardo; Johnson, Stephen B; Hausvater, Anaïs; Newman, Jonathan D; Berger, Jeffrey S; Bangalore, Sripal; Katz, Stuart D; Fishman, Glenn I; Kunichoff, Dennis; Chen, Yu; Ogedegbe, Gbenga; Hochman, Judith S
BACKGROUND:There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS:We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS:Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS:We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.
PMID: 32356628
ISSN: 1533-4406
CID: 4412912
Annals of vascular surgery. 2020:65:55-65.DOI: 10.1016/j.avsg.2019.10.055

High Prevalence and Mortality Associated with Upper Extremity Deep Venous Thrombosis in Hospitalized Patients at a Tertiary Care Center

Rokosh, Rae S; Ranganath, Neel; Yau, Patricia; Rockman, Caron; Sadek, Mikel; Berland, Todd; Jacobowitz, Glenn; Berger, Jeff; Maldonado, Thomas S
OBJECTIVE:MATERIAL AND METHODS: This is a single tertiary care center retrospective cohort study of all consecutive inpatients diagnosed with acute VTE from June 2015 to December 2015. During this period, 4495 patients underwent venous duplex examination (622 UE and 3873 LE), identifying 83 inpatient DVTs. Chronic DVT as well as those diagnosed in the outpatient population were excluded. DVTs were classified as either provoked or unprovoked. Provoked DVT were defined as the presence of any of the following factors within 30 days prior to diagnosis: major surgery, immobilization (greater than 3 days of bedrest), trauma, infection requiring antibiotics, central venous access, pregnancy, and/or hormonal medication use. Inpatient pulmonary embolisms (PE) detected on chest computed tomography (CT) were also evaluated during this time frame. Patient data were collected including age, gender, race, lifestyle factors, comorbidities, VTE risk factors, symptomatology at presentation, management including anticoagulation choice and filter placement if applicable, as well as discharge disposition. Statistical analysis was performed using GraphPad Prism 8.0 (GraphPad Software, San Diego, California, USA), and a threshold p-value of < 0.05 set for significance. RESULTS:During the study period, 83 DVTs (48 LEDVT, 35 UEDVT) and 24 PE were identified in 96 inpatients. Of these DVTs, 77.1% of these were defined as provoked. Eleven patients had simultaneous DVT and PE, and thirteen patients had PE with presumed occult pelvic or LEDVT. UEDVT patients had a higher proportion of comorbidities than LEDVT patients: coronary artery disease (25.7% vs. 13.1%, p=0.16), congestive heart failure (20% vs. 6.6%, p=0.09), as well as a trend toward higher incidence of malignancy (60% vs. 42.6%, p=0.13). Of provoked VTE, UEDVT correlated more significantly with central venous catheters (88.4% vs. 12.5%, p=<0.0001), but was less commonly associated with prolonged bed rest (19.2% vs. 39.5%, p=0.11). PE was diagnosed in 24/96 (25%) of the study population. Patients with LEDVT were found to have a significantly higher incidence of PE compared to those with UEDVT (34.4% vs. 8.6%, p=0.006). Same-admission mortality for patients with VTE was 13/96 (13.5%). Of these, patients with UEDVT had significantly higher all-cause mortality than patients with LEDVT (28.5% vs. 4.9%, p=0.004). When catheter-related UEDVT were excluded, there remained a significant difference in mortality between non-catheter related UEDVT and LEDVT (33.3% vs. 4.9% p=0.0119). CONCLUSIONS:This study demonstrates a high prevalence of UEDVT in hospitalized patients who experience VTE. Despite a lower incidence of synchronous PE, patients with UEDVT had a higher prevalence of significant medical comorbidities and higher all-cause mortality on the index hospital admission.
PMID: 31669473
ISSN: 1615-5947
CID: 4162582
New England journal of medicine. 2020:382(17):1608-1618.DOI: 10.1056/NEJMoa1915925

Management of Coronary Disease in Patients with Advanced Kidney Disease

Bangalore, Sripal; Maron, David J; O'Brien, Sean M; Fleg, Jerome L; Kretov, Evgeny I; Briguori, Carlo; Kaul, Upendra; Reynolds, Harmony R; Mazurek, Tomasz; Sidhu, Mandeep S; Berger, Jeffrey S; Mathew, Roy O; Bockeria, Olga; Broderick, Samuel; Pracon, Radoslaw; Herzog, Charles A; Huang, Zhen; Stone, Gregg W; Boden, William E; Newman, Jonathan D; Ali, Ziad A; Mark, Daniel B; Spertus, John A; Alexander, Karen P; Chaitman, Bernard R; Chertow, Glenn M; Hochman, Judith S; Abdallah, Abdallah M; Moreyra, Abel E; Laddu, Abhay A; Dubey, Abhishek; Goyal, Abhishek; Knighton, Abigail; Adeboye, Adedayo; Juceviciene, Agne; Urboniene, Agne; Szramowska, Agnieszka; Abdel-Latif, Ahmed; Ayoub, Ahmed; Elghamaz, Ahmed; Kamal, Ahmed; Talaat, Ahmed; Sharma, Ajay; Narula, Ajit Singh; Bagai, Akshay; Smigelskaite, Akvile; Raymond, Alain; Rheault, Alain; Loehr, Alaine Melanie; Varga, Albert; Maggioni, Aldo P; Moorman, Alec; Chevaile Ramos, Alejandro; Gisbert, Alejandro; Fratczak, Aleksandra; Laucevicius, Aleksandras; Chernyavskiy, Alexander M; Borisov, Alexander Sergeevich; Craft, Alexandra; Hunter, Alexandra; Hueb, Alexandre Ciappina; Schaan de Quadros, Alexandre; Muller, Alice Manica; Deiro, Aline Peixoto; Stone, Allegra; Castro, Almudena; Uxa, Amar; Van Craenenbroeck, Amaryllis; Roy, Ambuj; Kakkar, Amit; Flowers, Amy; Iskandrian, Amy; Djordjevic-Dikic, Ana D; Gomes Almeida, Ana; Francisco, Ana Rita; Mladenovic, Ana S; Santana, Ana; Lahiri, Anandaroop; Kuzmina-Krutetskaya, Anastasia M; Vamvakidou, Anastasia; Vertes, Andras; Gabriel, Andre; Bartykowszki, Andrea; Lorimer, Andrea; Pascual, Andrea; Coelho, Andreia; Rocha, Andreia; García-Rincón, Andrés; Starovoytov, Andrew; Łabyk, Andrzej; Kawakami, Anelise; Hoye, Angela; Nobre, Angelo; Acharya, Anjali; Anand, Anjali; Rishmawi, Anjana; Banfield, Ann; Luyten, Ann; Cichocka-Radwan, Anna; Fojt, Anna; Plachcinska, Anna; Teresinska, Anna; Webb, Anne Marie; Heath, Anne; Mathew, Anoop; Vega, Antonia; Carvalho, Antonio; Colombo, Antonio; Fiarresga, Antonio; Tharini, Anu; Rao, Anupama; Valdespino-Estrada, Aquiles; Diaz, Ariel; Asif, Arif; Seto, Arnold H; Campos-Santaolalla, Arturo S; Cheema, Asim N; Ahmed, Asker; Mathur, Atul; Leong, Audrey W; Ã…kerblom, Axel; Fuentes, Axelle; Naher, Aynun; Valaiyapathi, Badhma; Srinivasan, Balaji; Kaur, Baljeet; Bhargava, Balram; Guruge, Bandula; Wicklund, Barbara; Czarniak, Bartosz; Singh, Bebek; Igual, Begoña; Merkely, Bela; Shah, Benoy N; de Bruyne, Bernard; Abramson, Beth; Stefanchik, Beth; Harvey, Bethany; Shivalkar, Bharati; Malik, Bilal; Kurian, Binoy Mannekkattukudy; Hammouche, Bougrida; Beleslin, Branko D; Ferguson, Bruce; McManus, Bruce; Ascoli, Bruna Maria; Smith, Bryn; Allen, Byron J; Gibson, C Michael; Bairey Merz, C Noel; Pop, Calin; Gagné, Carl-Éric; Ohmart, Carly; Kartje, Carol M; Alsweiler, Caroline; Rodgers, Caroline; Spindler, Caroline; Gruber, Carolyn J; Albert, Catherine; Bone, Catherine; Lemay, Catherine; Kepka, Cezary; Suvarna, Chandini; Mercure, Chantale; Wiyarand, Charlene; Patel, Chetan; Attanasio, Chiara; Chow, Chi-Ming; Er, Ching Min; Ong, Ching-Ching; Manjunath, Cholenahally Nanjappa; Buller, Chris; Vassaliere, Christel; Vrints, Christiaan; Witzke, Christian; Ballantyne, Christie; Björklund, Christina; Roraff, Christine; Laure, Christophe; Thuaire, Christophe; Chan, Christopher; Fordyce, Christopher; Kinsey, Christopher; Xia, Chunli; Schultz, Cidney; Held, Claes; Cortés, Claudia; Escobar, Claudia; Freixo, Cláudia; Kadalie, Clemens T; Thobois, Corine; Page, Courtney; Bare, Cristina; Espinosa, Dalisa; Gao, Dan; Rizk, Dana; Puzhevsky, Daniela; Analyst, Data; Charytan, David M; Williams, David O; Booth, David; Charytan, David; Cohen, David; DeMets, David; Foo, David; Goldfarb, David; Schlichting, David; Sisson, David; Taggart, David; Waters, David; Wheeler, David; Williams, David; Vo, Davis; Teodorczyk, Dawid; Shelstad, Dawn D; Kereiakes, Dean; Yip, Deborah; Ramaswamy, Deepa; Mattina, Deirdre; Murphy, Deirdre; Jiang, Dengke; Cyr, Derek; Cukali, Diana; Camara, Diane; Stournaras, Dimitrios; Patel, Dipti; Li, Dongze; Exley, Donna; Reimann, Doreen; Schwartz, Doron; Cacela, Duarte; Conway, Dwayne S G; Punnoose, Eapen; Tay, Edgar L; Karanjah, Edgar; Gomes Lima, Eduardo; Hernandez-Rangel, Eduardo; Nicol, Edward D; Kaczmarska, Edyta; Refoyo Salicio, Elena; Feen, Eli; Durán-Cortés, Elihú; Janzen, Elisabeth M; van Dongen, Elise; Restelli Piloto, Elissa; Srbinovska Kostovska, Elizabeta; Capasso-Gulve, Elizabeth; Zbyshevskaya, Elizaveta V; Fridell, Ellie; Lader, Ellis W; Gosmanova, Elvira; Tachot, Emilie; Howard, Emma; Sorbets, Emmanuel; Alonso-Álvarez, Encarnación; Daugas, Eric; Alexánderson Rosas, Erick; Montpetit, Estelle; Passamani, Eugene; Shutov, Evgeny; Szczerba, Ewa; Wojtala, Ewelina; Ribeiro Silva, Expedito Eustáquio; Fimiani, Fabio; Hage, Fadi; Jafary, Fahim Haider; Feng, Fang; Ranjbaran, Fatima; Pinto, Fausto J; Caeiro, Fernando; Nolasco, Fernando; Silva, Filipa; Ottani, Filippo; Al Solaiman, Firas; Egydio, Flávia; Chereches, Florina; De Micco, Francesca; Bianchini, Francesca; Pietrucci, Francesca; Orso, Francesco; Pisano, Francesco; Patuleia Figueiras, Francisca; Madore, François; Harrell, Frank; Rockhold, Frank; Van de Werf, Frans; Guenther, Franziska; Mohr, Fred; Karthikeyan, G; Galeote, Gabriel; Grossmann, Gabriel; Steg, Gabriel; Guzman, Gabriela; Gabrielli, Gabriele; Chen, Gang; Sharma, Gautam; Petty, Gaylin; Mikolaitiene, Gelmina; Yee, Gennie; Devlin, Gerard Patrick; Esposito, Gerard; Ágoston, Gergely; Lamas, Gervasio; Cobb, Gia; Perna, Gian Piero; Leone, Gianpiero; Mishra, Girish; Barge-Caballero, Gonzalo; Young, Grace M; Scaro, Graciela; Wong, Graham; Pressman, Gregg; Simonis, Gregor; Steinmaurer, Gudrun; Portugal, Guilherme; Cantinho Lopes, Guilhermina; Garcia-Garcia, Guillermo; Wang, Guoqin; Wander, Gurpreet S; Gulati, Gurpreet; Zhang, Haibo; Marciniak, Halina; Dai, Hao; Dong, Haojian; Franch, Harold; White, Harvey; Elabd, Hatem; Pomeroy, Hayley; Golden, Heather; Wilson, Heidi; Abergel, Helene; Siddaram, Hemalata; Mahapatra, Hemant Shakhar; Stokes, Henry C; Osseni, Hermine; Schuchlenz, Herwig; Skali, Hicham; Mattix-Kramer, Holly; Cheng, Hong; Mahrous, Hossam; Pejkov, Hristo; Marques, Hugo; Zhong, Hui; El Fishawy, Hussien; Webb, Ian; Kullo, Iftikhar; Grazhdankin, Igor O; Hassan, Ikraam; Pina, Ileana L; Tamasauskiene, Ilona; Cabrita, Inês Zimbarra; Rodrigues, Ines; Soveri, Inga; Mitevska, Irena Peovska; Lang, Irene Marthe; Subbotina, Irina; Kalibataite-Rutkauskiene, Irma; Roy, Isabelle; Tejani, Ishita; Naryshkin, Ivan A; Jankovic, Ivana; Niedzwiecka, Iwona; Kusmierek, Jacek; Chow, Jackie; Heo, Jaekyeong; Maksym, Jakub; Davies, James E; Jang, James J; Hirsch, James; Tatoulis, James; Henzel, Jan; Oliveira, Janaina; Rangaswami, Janani; Eckstein, Jane; Raj, Janitha; Pozzibon, Jaqueline; Drozdz, Jaroslaw; Kwok Kong, Jason Loh; Call, Jason T; Linefsky, Jason; Garcia, Javier J; Meisner, Jay; Scales, Jayne; Juliard, Jean Michel; Diodati, Jean; Juliard, Jean-Michel; Russo, Jeanne; Schoep, Jeannette J M; Leimberger, Jeff; Milliken, Jeffrey C; Anderson, Jeffrey; Kanters, Jeffrey; Lorin, Jeffrey; Moses, Jeffrey; Stepanovic, Jelena J; Celutkiene, Jelena; Stojkovic, Jelena; Jose, Jenne M; Stanford, Jennifer L; Hogan, Jennifer; Horst, Jennifer; Isaacs, Jennifer; Thomson, Jennifer; Tomfohr, Jennifer; White, Jennifer; Yee, Jerry; Berg, Jessica; Peteiro, Jesus; Peteiro, Jesús; Li, Jia; Liu, Jiamin; Zhang, Jianxin; Marcus, Jill; Blankenship, Jim; Dong, Jing; Chen, Jiyan; Evans, Jo; Peñafiel, Joaquín V; Sabik, Joe; Christopher, Johann; Kostis, John B; Graham, John Joseph; Doan, John; Jose, John; Kotter, John; Lehman, John; Middleton, John; Pownall, John; Gleadle, Jonathan M; Chavez-Iñiguez, Jonathan S; Byrne, Jonathan; Himmelfarb, Jonathan; Lebowitz, Jonathan; Thorsen, Jonean; Carrillo Calvillo, Jorge; Escobedo, Jorge; Ortega-Ramírez, José A; Cuenca-Castillo, José J; Diez, Jose L; Narro Villanueva, José Luis; da Costa Vieira, José Luiz; Flores-Palacios, José M; Fragata, Jose; Lopes, Jose; Lopez-Sendon, Jose; Lopez-Sendon, José; Rueda, Jose; Selvanayagam, Joseph B; Sacco, Joseph; Loh, Joshua P; Burkhardt, Joy; López Quijano, Juan Manuel; Gaztanaga, Juan; Sebo, Judit; Wright, Judith; Stumpf, Juergen; de Aveiro Morata, Julia; Figal, Julio César; Hernandez Jaras, Julio; Yang, Junqing; Garg, Jyotsna; Rani, K Manjula; Preethi, K; Goetschalckx, Kaatje; Calfas, Karen; Petrosyan, Karen; Servilla, Karen; Swan, Karen; Ploetze, Karin; Kryczka, Karolina; Wojtczak-Soska, Karolina; Wojtera, Karolina; Ramasamy, Karthik; Łuczak, Katarzyna; Malinowska, Katarzyna; Knaut, Katharina; Martin, Katherine; Claes, Kathleen; Mason, Kathryn; Mahaffey, Ken; Gin, Kenneth; Lee, Kerry; Bonin, Kerstin; Mikes, Kerstin; Bainey, Kevin R; Harley, Kevin T; Marzo, Kevin; McMahon, Kevin; Abdul-Nour, Khaled; Alfakih, Khaled; Dajani, Khaled; Kushniriuk, Khrystyna; Poh, Kian-Keong; Holland, Kim; Halverson, Kimberly E; Murphy, Kinnari; Reddy, Kiran; Quiles, Kirsten J; Abercrombie, Kirsty; Matschke, Klaus; Szymczyk, Konrad; Chan, Koo Hui; Mavromatis, Kreton; Hongalgi, Krishnakumar; Thygesen, Kristian; Salmi, Kristin M; Newby, Kristin; Arges, Kristine; Teoh, Kristine; Drzymalski, Krzysztof; Kumbar, Lalathaksha; Matics, Laszlone; Hickson, LaTonya J; Keinaite, Laura; Sarti, Laura; True, Laura; Phillips, Lawrence M; Friedman, Lawrence; Maranan, Leandro C; Lotaif, Leda; Dharmarajan, Lekshmi; Bockeria, Leo A; Pizzol Caetano, Leonardo; Bridi, Leonardo; Bershtein, Leonid L; Yan, Li Hai; Li, Li; Sousa, Lidia; Xu, Lihong; Zhang, Lihua; Zhang, Lili; Mazza Barbosa, Lilian; Tozija, Liljana; Arcand, Linda; Patricio, Lino; Zhang, Liping; Hatch, Lisa; Jiang, Lixin; Low, Liz; Salman, Loay; Lopez, Lorena; Pritchard, Lori; Bernanrdes, Luis; Guzman, Luis; Teo, Lynette L; Reddy, M Sowjanya; Simoons, Maarten; Konigstein, Maayan; Selas, Mafalda; Madero, Magdalena; Miller, Magdalena; Misztal-Teodorczyk, Magdalena; Abdelhamid, Magdy; Fahim, Magid; Mylarappa, Mahevamma; Joseph, Majo X; Frach, Malgorzata; Rani, Manjula; Galvani, Marcello; Demkow, Marcin; Szkopiak, Marcin; De Fabritis, Marco; Magnoni, Marco; Marini, Marco; Sicuro, Marco; Roik, Marek; Alfonso, Maria A; Pereira de Moraes, Maria Antonieta; Martínez-Ruíz, María Dolores; Canziani, Maria Eugenia; Martin, Maria Eugenia; Caetano, Maria Inês; Corral, Maria P; Pérez García, Maria; Andreasson, Maria; Posada, Maria; Dracoulakis, Marianna D A; Rubio, Mariano; Petrovic, Marija T; Vieira, Marina; Garcia, Mario J; D'arezzo, Mario; Orgera, Maris; Miglinas, Marius; Garand, Mark; Peterson, Mark; Xavier, Mark; Mosley, Marlowe; Capinha, Marta; Swiderek, Marta; Meyer, Martha; Ceseri, Martina; Tricoli, Martinia; Wiilliams, Mary; Champagne, Mary Ann; Streif, Mary; Leesar, Massoud; Claudia, Matei; Solecki, Mateusz; Mungo, Matías Nicolás; Shinseki, Matthew; Weir, Matthew; Nédio, Maura Carina; Winter, Max-Paul; Krishnam, Mayil S; Mishra, Meenakshi; Hwang, Mei; Srilatha, Melemadathil; LeFevre, Melissa; Simegn, Mengistu; Gibson, Michael A; Rubens, Michael B; Shapiro, Michael D; Chobanian, Michael; Davidson, Michael; Farkouh, Michael; Mack, Michael; Wlodarczyk, Michal; Khouri, Michel G; Crowder, Michelle; Ratliff, Michelle; Borges Santos, Miguel; Nobre Menezes, Miguel; Perez Fontan, Miguel; Barrero, Miguel; Tapolyai, Mihaly; Torosoff, Mikhail T; Dobric, Milan R; Gadkari, Milind Avdhoot; Kyaw, Min Tun; Revivo, Miri; Lustre, Mitchel B; Adel, Mohamed; Hassan, Mohamed; El-Hajjar, Mohammad; Hussain, Mohammed; Saleem, Mohammed; Blanco-Calvo, Moisés; Jiménez-Santos, Moisés; Laukyte, Monika; Saric, Muhamed; Takiuti, Myrthes Emy; Asif, Nadia; Moorthy, Nagaraja; Ogletree, Naima L; Katamadze, Nana O; Nataraj, Nandita; Uchida, Naomi; Ismail, Nasrul; Oliveira, Natalia S; de Carvalho Maffei, Natalia; Brosens, Nathalie; Aslam, Naved; Akhtar, Naveed; Mowafy, Neamat; Pandit, Neeraj; Parakh, Neeraj; Pannu, Neesh; Duncan, Neill; Garcevic, Nevena; Meadows, Ngaire; Danchin, Nicholas; Deming, Nicole; Boskovic, Nikola N; Karogiannis, Nikolaos; Zhang, Ning; Kumar, Nirmal; Sharma, Niruta; Chadha, Nitika; Naik, Nitish; Durfee, Noelle M; Cosgrove, Nora M; Urbanski, Norbert; Hogg, Norma; 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Pruszczyk, Piotr; Loh, Poay-Huan; Samadi, Pouneh; Deedwania, Prakash; Patel, Pranav M; Polamuri, Praneeth; Sharma, Pratiksha; Kamath, Preeti; Thomas, Prince; Arambam, Priyadarshani; Sodhi, Puneet; Naik, Pushpa; Zhong, Qi; Zhao, Qian; Yuan, Qianqian; Xie, Qiulan; Murphy, Rachel; Lyubarova, Radmila; Lyubarova, Radmilar; Fisher, Raewyn; Diaz, Rafael; Maldonado, Rafael; Selgas, Rafael; Bugiardini, Raffaele; Chaudhry, Rafia; Kavalakkat, Raisa; Vs, Rajalekshmi; Nair, Rajesh Gopalan; Narang, Rajiv; Yadav, Rakesh; Carvalho, Ramiro; Jesús-Pérez, Ramon de; Leng, Ran; Kachru, Ranjan; Sanchez, Raquel; Dwyer, Raven R; Lee, Raven; Wyman, Ray; Wong, Raymond C; Hampson, Reinette; Karam Kalil, Renato Abdala; Lopes, Renato D; Eick, Renato George; Lopes, Renato; Ravindran, Reshma; Gamma, Reto Andreas; Costa, Ricardo; Bhatt, Richa; Trimlett, Richard H J; Patel, Risha; Coram, Rita; Riezebos, Robert K; Donnino, Robert M; Guyton, Robert; Harrington, Robert; Malecki, Robert; Favaloro, Roberto René; Elliott, Robyn; Lima, Rodolfo G S D; Tandon, Rohit; Doerr, Rolf; Tewari, Roma; Wald, Ron; Hu, Rongrong; Collins, Rory; Mehran, Roxana; Senior, Roxy; Baleón-Espinosa, Rubén; Ramos, Ruben; Ferreira, Rui; Kirby, Ruth; Pérez-Fernández, Ruth; Ramakrishnan, S; Dwivedi, S K; Lubna, Sadath; Ahmed, Sadiq; Govindan, Sajeev Chakanalil; Alfalahi, Salamah; Cruz-Flores, Salvador; Costa, Salvatore P; Setty, Sampoornima; Nwosu, Samuel; Mahajan, Sandeep; Seth, Sandeep; Singh, Sandeep; Niehe, Sander R; Carr, Sandy; Ogrizovic, Sanja Simic; Ogrizovic, Sanja; Gulati, Sanjeev; Sharma, Sanjeev; Fernandez, Sara; Williams, Sarah; Ralhan, Sarju; Kedev, Sasko; Singh, Satinder; Sankaranarayanan, Satish; Manjunath, Satvic Cholenahally; Lee, Sau; Thaxton, Schawana; O'Brien, Sean M; Sobczak, Sebastian; Nour, Seema; Sayganov, Sergey A; Bravo Baptista, Sérgio; Draibe, Sergio; Sokol, Seth; Chandra, Sharad; Mackedanz, Shari; Goodman, Shaun; Shirazian, Shayan; Karwa, Sheetal Rupesh; Ussery, Sheri; Bajaj, Sheromani; Heydari, Shirin; Choudhary, Shiv Kumar; 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Ye, Zhiming; Yu, Zixiang; Davidovits, Zoltan; Petronijevic, Zvezdana
BACKGROUND:Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS:We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS:At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P = 0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P = 0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P = 0.03). CONCLUSIONS:Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).
PMID: 32227756
ISSN: 1533-4406
CID: 5451232
New England journal of medicine. 2020:382(15):1395-1407.DOI: 10.1056/NEJMoa1915922

Initial Invasive or Conservative Strategy for Stable Coronary Disease

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Tamis-Holland, Jacqueline E; Fannon, Jacqueline; Quin, Jacquelyn A; Do, Jacquelyn; Heo, Jaekyeong; Maksym, Jakub; Davies, James E; O'Keefe, James H Jr; Jang, James J; Cha, James; Harrison, James; Hirsch, James; Stafford, James; Tatoulis, James; Rankin, Jamie; Henzel, Jan; Orga, Jan; Tancredi, Jana; Oliveira, Janaina; Burton, Jane; Eckstein, Jane; Marucci, Jane; Knight, Janet P; Blount, Janet; Halliday, Janet; Kourzenkova, Janetta; Raj, Janitha; Sinning, Jan-Malte; Pozzibon, Jaqueline; Drozdz, Jaroslaw; Karwowski, Jaroslaw; Glover, Jason D; Kwok, Jason Loh; Call, Jason T; Linefsky, Jason; Gomes, Jassira; Anumpa, Jati; Garcia, Javier J; Courtis, Javier; Meisner, Jay; Jayakumar, K; Scales, Jayne; Denaro, Jean E; Juliard, Jean Michel; Ho, Jean; Stansborough, Jeanette K; Juliard, Jean-Michel; Russo, Jeanne; Schoep, Jeannette J M; Thambyrajah, Jeet; Leimberger, Jeff; Breall, Jeffery A; Kohn, Jeffrey A; Milliken, Jeffrey C; Anderson, Jeffrey; Blume, Jeffrey; Kanters, Jeffrey; Lorin, Jeffrey; Moses, Jeffrey; Stepanovic, Jelena J; Celutkiene, Jelena; Djokic, Jelena; Stojkovic, Jelena; Jose, Jenne M; Manchery, Jenne; Mull, Jennifer A; Czerniak, Jennifer H; Stanford, Jennifer L; Gillis, Jennifer; Horst, Jennifer; Isaacs, Jennifer; Langdon, Jennifer; Thomson, Jennifer; Tomfohr, Jennifer; White, Jennifer; Kuo, Jen-Yuan; Rautureau, Jeremy; Fleg, Jerome; Berg, Jessica; Rodriguez, Jessica; Waldron, Jessica; Patro, Jhina; Li, Jia; Mao, Jiajia; Liu, Jiamin; Wang, Jian'an; Li, Jianhua; Zhang, Jianxin; Qi, Jie; Lyo, Jihyun; Marcus, Jill; Blankenship, Jim; Zhang, Jing; Liu, Jingjing; Fan, Jing-Yao; Li, Jiun-Yi; Pradhan, Jiwan; Chen, Jiyan; Rivera Caravaca, J M; Evans, Jo; Garcia Picart, Joan; Hecht, Joan; Jaroch, Joanna; Zalewska, Joanna; Kelly, Joanne; Taaffe, Joanne; Abbud, João Reynaldo; Vitola, João V; Peñafiel, Joaquín V; Benatar, Jocelyne; Bindeman, Jody; Sabik, Joe; Klitch, Joel; Christopher, Johann; Aspberg, Johannes; Friedman, John D; Beltrame, John F; Heitner, John F; Graham, John Joseph; Davies, John R; Doan, John; Kotter, John; Kurian, John; Mukai, John; Pownall, John; Sobolewska, Jolanta; Kobashigawa, Jon; Goldberg, Jonathan L; Bazeley, Jonathan W; Byrne, Jonathan; Himmelfarb, Jonathan; Leipsic, Jonathan; Thorsen, Jonean; Trejo Gutierrez, Jorge F; Escobedo, Jorge; Timmer, Jorik; Ortega-Ramírez, José A; Marin-Neto, José Antonio; Salas, Jose D; Castillo, Jose Enrique; Saraiva, Jose Francisco; Cuenca-Castillo, José J; Diez, Jose L; Narro Villanueva, José Luis; da Vieira, José Luiz; Flores-Palacios, José M; Gonzalez, Jose Ramon; Seijas Amigo, Jose; Fragata, Jose; Padró, Josep Maria; McGarvey, Josheph F X Jr; Hannan, Joseph; Sacco, Joseph; Sweeny, Joseph; Wiesel, Joseph; Abraham, Josephine D; Loh, Joshua P; Burkhardt, Joy; White, Joyce R; Riestenberg-Smith, Joyce; Sebo, Judit; Meadows, Judith L; Wright, Judith; Foltz, Judy Mae; Hung, Judy; Otis, Judy; Stumpf, Juergen; Tsai, Jui-Peng; Dionne, Julia S; de Aveiro Morata, Julia; Bunke, Julie; Morrow, Julie; Figal, Julio César; Fujita, Jun; Jiang, Jun; Li, Junhua; Yang, Junqing; Euathrongchit, Juntima; Garg, Jyotsna; Manjula Rani, K; Preethi, K; Goetschalckx, Kaatje; Eggers, Kai; Surineni, Kamalakar; Hirase, Kanae; Kapilamoorthy, T R; Calfas, Karen; Gratrix, Karen; Hallett, Karen; Hultberg, Karen; Nugent, Karen; Petrosyan, Karen; Swan, Karen; Kryczka, Karolina; Wojtczak-Soska, Karolina; Wojtera, Karolina; Lenk, Karsten; Ramasamy, Karthik; Łuczak, Katarzyna; Malinowska, Katarzyna; Pointon, Kate; Robb, Kate; Martin, Katherine; Claes, Kathleen; Carruthers, Kathryn; Siegel, Kathy E; Drouin, Katia; Fowler-Lehman, Katie; Rawat, Kavita; Rowe, Kay; Fukuda, Keiichi; Fox, Keith A A; Mahaffey, Ken; Unterbrink, Kendra; Giedd, Kenneth; Van Loo, Kerrie; Lee, Kerry; Bonin, Kerstin; Bainey, Kevin R; Harley, Kevin T; Anstrom, Kevin; Chan, Kevin; Croce, Kevin; Landolfo, Kevin; Marzo, Kevin; Patel, Keyur; Abdul-Nour, Khaled; Alfakih, Khaled; Dajani, Khaled; Ziada, Khaled; Baloch, Khaula; Kushniriuk, Khrystyna; Poh, Kian-Keong; Ireland, Kim F; Holland, Kim; Byrne, Kimberly Ann; Halverson, Kimberly E; Elmore, Kimberly; Miller-Cox, Kimberly; Reddy, Kiran; Quiles, Kirsten J; Abercrombie, Kirsty; Matschke, Klaus; Szymczyk, Konrad; Chan, Koo Hui; Preethi, Kotiboinna; Sokhon, Kozhaya; Meemuk, Krissada; Thygesen, Kristian; Salmi, Kristin M; Newby, Kristin; Wippler, Kristina; Arges, Kristine; Teoh, Kristine; Etherington, Krystal; Łoboz-GrudzieÅ„, Krystyna; Reczuch, Krzysztof W; Bury, Krzysztof; Drzymalski, Krzysztof; KukuÅ‚a, Krzysztof; Sung, Kuo-Tzu; Huber, Kurt; Douangvila, Ladda; Sullenberger, Lance; Trama, Larissa Miranda; Matics, Laszlone; Drew, Laura; Flint, Laura; Keinaite, Laura; Sarti, Laura; Kolakaluri, Laurel; Phillips, Lawrence M; Friedman, Lawrence; Phillips, Lawrence; Velicki, Lazar; Howell, Leah; Maranan, Leandro C; Cox, Leanne; Daba, Ledjalem; Zhang, Lei; Dharmarajan, Lekshmi; Bockeria, Leo; Pizzol Caetano, Leonardo; Bridi, Leonardo; Bershtein, Leonid L; Sokalski, Leszek; Yan, Li Hai; Li, Li; Nijmeijer, Lia; Sousa, Lidia; Xu, Lihong; Zhang, Lihua; Zhang, Lili; Schiavi, Lilia; Barbosa, Lilian Mazza; Khor, Lillian L; Felix-Stern, Lina; Hall, Linda L; Hollenweger, Linda M; Arcand, Linda; Davidson-Ray, Linda; Schwarz, Linda; Sikora, Lindsey N; Chi, Lingping; Patricio, Lino; Zhang, Liping; Chaytor, Lisa; Hatch, Lisa; McCloy, Lisa; Wong, Lisa; Persson, Liselotte; Jiang, Lixin; Low, Liz; Pupic, Ljiljana; Bière, Loïc; Monti, Lorenzo; Christensen, Lori; Pritchard, Lori; Black, Loriane; Desimone, Lori-Ann; Larmand, Lori-Ann; McGregor, Lorraine; Morby, Louise; Thomson, Louise; Harvey, Luc; de Pádua Baptista, Luciana; Garcia, Lucilla; Eliahou, Ludivine; Helmer, Ludmila; Smidt, Luis F; Bernanrdes, Luis; Guzman, Luis; Carvalho, Luiz A; Xiong, Luyang; Teo, Lynette L; Neeson, Lynn M; Winstanley, Lynne; Srichai-Parsia, M Barbara; Quintana Giner, M; Sowjanya Reddy, M; Valdés Chávarri, M; Grazia Rossi, M; Simoons, Maarten; Konigstein, Maayan; Lesiak, Maciej; Olsowka, Maciej; Selas, Mafalda; Corfias, Magalie; Madero Rovalo, Magdalena; Łanocha, Magdalena; Miller, Magdalena; Misztal-Teodorczyk, Magdalena; Rantinella, Magdalena; Abdelhamid, Magdy; Jimenez, Magnolia; Alam, Mahboob; Mylarappa, Mahevamma; El Shahawy, Mahfouz; Mohamed, Mahmoud; Al-Bustami, Mahmud; Joseph, Majo X; Frach, Malgorzata; CeliÅ„ska-Spodar, MaÅ‚gorzta; Helm, Malte; Chacko, Manas; Murphy, Mandy; Vinod, Manitha; Rani, Manjula; Dhawan, Manu; Mombelli, Manuela; Weber, Marcel; Galvani, Marcello; Rodrigues, Marcelo Jamus; Dubin, Marcia F; Werner Bayer, Marcia F; Szkopiak, Marcin; Monsalve, Marco Antonio; Santos, Marco Bizzaro; Magnoni, Marco; Marini, Marco; Sicuro, Marco; Zenati, Marco; Coimbra Resende, Marcos Valério; Roik, Marek; Bentzvi, Margalit; Gilsenan, Margaret; Iraola, Margaret; Quinn, Margot C; Alfonso, Maria A; Pereira Moraes, Maria Antonieta; Martínez-Ruíz, María Dolores; Canales, María Fernanda; Caetano, Maria Inês; Corral, Maria P; Pérez García, Maria; Actis, Maria Victoria; Aguirre, Maria; Andreasson, Maria; Aprile, Maria; Colton, Maria; Martin, Maria Eugenia; Lasala, Maria; Lorenzo, Maria; Posada, Maria; Shier, Maria; Thottam, Maria; Furtado, Mariana V; Okada, Mariana Yumi; Dracoulakis, Marianna D A; De Andrade, Marianne; Rubio, Mariano; Essermark, Marie; Scherrer-Crosbie, Marielle; Petrovic, Marija T; Zdravkovic, Marija; Black, Marilyn; Garcia, Marina; Garcia, Mario J; Szulik, Mariola; Orgera, Marisa; de Belder, Mark A; Harbinson, Mark; Hyun, Mark; Peterson, Mark; Xavier, Mark; Mosley, Marlowe; Capinha, Marta; Marcinkiewicz-Siemion, Marta; Swiderek, Marta; Meyer, Martha; Ceseri, Martina; Tricoli, Martina; Kronenberg, Marvin; Williams, Mary; Champagne, Mary Ann; Rogge, Mary Colleen; Soltau, Mary R; Streif, Mary; Villella, Massimo; Leesar, Massoud; Claudia, Matei; Solecki, Mateusz; Mungo, Matías Nicolás; Wall, Matthew Jr; Budoff, Matthew; Jezior, Matthew; Luckie, Matthew; Friedrich, Matthias; Haeffner, Mauren P; Tscharre, Maximilian; Winter, Max-Paul; Almeida, Mayana; Krishnam, Mayil S; Patel, Mayuri; Mishra, Meenakshi; Manocchia, Megan; Kakade, Meghana; Munro, Melanie J; Chaplin, Melissa D; LeFevre, Melissa; Andiapen, Mervyn; Gibson, Michael A; Rubens, Michael B; Turner, Michael C; Shapiro, Michael D; Lee, Michael W; Berlowitz, Michael; Davidson, Michael; Mack, Michael; McDaniel, Michael; Mumma, Michael; Wlodarczyk, Michal; Khouri, Michel G; Slama, Michel S; Rawlins, Michele; Bonner, Michelle M; Seib, Michelle M; Chang, Michelle; Crowder, Michelle; Dixon, Michelle; Mayon, Michelle; McEvoy, Michelle; Yee, Michelle; Fernandes, Miguel M; Nobre Menezes, Miguel; Souto Bayarri, Miguel; Barrero, Miguel; Torosoff, Mikhail T; Dobric, Milan R; Dobric, Milan; Dekleva, Milica Nikola; Gadkari, Milind Avdhoot; Gomez, Millie; Kyaw, Min Tun; Brooks, Miriam; Stevo Martinovic, Miroslav; Lustre, Mitchel B; Vakani, Mohammad Tariq; El-Hajjar, Mohammad; Al-Amoodi, Mohammed; Hussain, Mohammed; Saleem, Mohammed; Blanco-Calvo, Moisés; Jiménez-Santos, Moisés; Bhatia, Mona; Rosca, Monica; Laukyte, Monika; Gracida Blanca, Montserrat; Vila Perales, Montserrat; Al-Mallah, Mouaz H; de Oliveira Filho, Moysés; Ntsekhe, Mpiko; Saric, Muhamed; Chen, Mulei; Brousseau, Myriam; Takiuti, Myrthes Emy; Cemerlic-Adjic, Nada; Asif, Nadia; Gakou, Nadia; Hussain, Nafisa; Katamadze, Nana O; Clapp, Nancy L; Aedy, Nancy; Nataraj, Nandita; Wenger, Nanette K; Uchida, Naomi; Ismail, Nasrul; Oliveira, Natalia S; de Carvalho Maffei, Natalia; Spitzer, Natalie; Putnam, Natasha C; Aslam, Naved; Mowafy, Neamat; Pandit, Neeraj; Parakh, Neeraj; Garcevic, Nevena; Meadows, Ngaire; Tran, Nhi N; Danchin, Nicholas; Lakeman, Nicki; Johnston, Nicola; Shammas, Nicolas W; Saint Vrestil, Nicole; Deming, Nicole; Zhong, Nier; Patel, Niket; Boskovic, Nikola N; Karogiannis, Nikolaos; Werner, Nikos; Johnston, Nina; Zhang, Ning; Zhou, Ning; Hindoyan, Niree; Kumar, Nirmal; Chadha, Nitika; Naik, Nitish; Aripova, Nodira; Mtana, Noloyiso; Eskelson, Nona A; Mokhtar, Noor Syamira; Taksaudom, Noppon; Basri, Nor Asiah; Marchelletta, Nora; Hogg, Norma; Jungla, Nungshi; Ferreira, Nuno; Lubyanaya, Oksana A; Nikolaeva, Olga B; Cañavate, Olga; Sobrino, Olga; Walesiak, Olga; Walter, Olga; ZdoÅ„czyk, Olga; Lim, Olivia J; Anaya, Olivia; Mancilla, Olivia; Dubourg, Olivier; Bello, Olugbenga; Almousalli, Omar; Thompson, Omar; Olurinde, Oni; Harel, Or; Raheem, Osama; Méndiz, Oscar; Prada-Delgado, Óscar; Shapira, Oz; Schulze, P Christian; Panpunuan, Pachara; Maurovich-Horvat, Pal; Garg, Pallav; Moraga, Paloma; Singh, Pam; Julian, Pamela; Ouyang, Pamela; Sigel, Pamela; Woodard, Pamela; Zhou, Panpan; Poggio, Paola Emanuela; Smanio, Paola; Calabro, Paolo; Jeetley, Paramjit; Goube, Pascal; Nguyen, Patricia K; Alarie, Patricia; Arakelian, Patricia; Arsenault, Patricia; Blaise, Patricia; Brito, Patricia; Cowper, Patricia; Endsley, Patricia; Mieses, Patricia; Alexander, Patrick B; Donnelly, Patrick; Wilmot, Patrick; Lebioda, Patrycja; Gordon, Paul C; Mesropian, Paul Der; Galiwango, Paul; Hauptman, Paul; Kennedy, Paul; Beardsley, Paula; García-González, Paula; Rezende, Paulo Cury; Caramori, Paulo Ricardo; Kozlov, Pavel S; Canas Silva, Pedro; Melo Barros E Silva, Pedro Gabriel; Píccaro de Oliveira, Pedro; Carvalho, Pedro; Modas, Pedro; Rio, Pedro; Jain, Peeyush; He, Peiyu; McCullough, Peter A; Stone, Peter H; Pollak, Peter M; Douglass, Peter; Henriksen, Peter; OKane, Peter; Ong, Peter; Jones, Philip; Rogal, Philip; Généreux, Philippe; Menasche, Philippe; Rheault, Philippe; Goold, Phoebe; Gervais, Pierre; Michaud, Pierre; Calvillo, Pilar; Chai, Ping; Jakubowski, Piotr; Pruszczyk, Piotr; Slomka, Piotr; Sritara, Piyamitr; Loh, Poay-Huan; Sonawane, Poonam; Samadi, Pouneh; Parikh, Pragnesh P; Deedwania, Prakash; Patel, Pranav M; Polamuri, Praneeth; Sharma, Pratiksha; Vasquez, Precilia; Kamath, Preeti; Thomas, Prince; Arambam, Priyadarshani; Mehta, Puja K; Grant, Purvez; Naik, Pushpa; Zhong, Qi; Zhao, Qian; Zhou, Qiang; Yuan, Qianqian; Yu, Qin; Li, Qingxian; Xie, Qiulan; Zeng, Qiutang; Vindhya, R J; Gerlach, R James; King, Rachel; Vučić, Rada; Lyubarova, Radmila; Pracon, Radoslaw; Fisher, Raewyn; Beyar, Rafael; Diaz, Rafael; Selgas, Rafael; Bugiardini, Raffaele; Fanelli, Raffaele; Kavalakkat, Raisa; Rajalekshmi, V S; Barua, Rajat S; Menon, Rajeev; Nair, Rajesh Gopalan; Francis, Rajesh; Narang, Rajiv; Yadav, Rakesh; Huston, Ralph Alan; Ramakrishnan, T; de Silva, Ramesh; Mahmoud, Rami El; Carvalho, Ramiro; de Jesús-Pérez, Ramon; Stevens, Ramona; Leng, Ran; Kachru, Ranjan; Nath, Ranjit Kumar; Sanchez, Raquel; Dwyer, Raven R; Lee, Raven; Wyman, Ray; Wong, Raymond C; Little, Raymond W; Ocaranza Sanchez, Raymundo; Wimmer, Rebecca J; Bariciano, Rebecca; Otis, Rebecca; Herrmann, Rebekah R; Yunis, Reem; Hampson, Reinette; Karam, Renato Abdala; Hessian, Renee C; Kaneshiro, Renee; Ravindran, Reshma; Gamma, Reto Andreas; Bhandari, Reyna; Arsanjani, Reza; Lopes, Ricardo L; Mendes Oliveira, Ricardo; Costa, Ricardo; Bhatt, Richa; Davies, Richard F; Trimlett, Richard H J; Goldweit, Richard; Hermanides, Rik; Nakanishi, Rine; Sidh, Rinu R; Patel, Risha; Coram, Rita; Siddiqui, Rizwan A; Beanlands, Rob S; Hamburger, Robert J; Riezebos, Robert K; Donnino, Robert M; Bojar, Robert; Chilton, Robert; Guyton, Robert; Henderson, Robert; Kornberg, Robert; Leber, Robert; Mao, Robert; Stenberg, Robert; Santos, Roberta P; Favaloro, Roberto René; Amati, Roberto; Lima, Rodolfo G S D; Cerci, Rodrigo J; Tumelero, Rogerio; Tandon, Rohit; Tewari, Roma; Miranda-Peats, Romalisa; Wald, Ron; Mastouri, Ronald A; Morford, Ronald G; Schwartz, Ronald G; Pedalino, Ronald P; Hu, Rongrong; Hansen, Ronnell A; Cohen, Ronny A; Hachamovitch, Rory; Homem, Rosa; Sandonato, Rosa; Laimer, Rosane; Gans, Rosann; Yost, Roxanne; Mathew, Roy; Baleón-Espinosa, Rubén; Ramos, Ruben; Gevorgyan, Rubine; Ferreira, Rui; Jing, Rui; Pérez-Fernández, Ruth; Dwivedi, S K; Ramakrishnan, S; Khan, Saadat; Bokhari, Sabahat; Thomas, Sabu; Lubna, Sadath; Khan, Sajeeda Parveen; Govindan, Sajeev Chakanalil; Girotra, Saket; Kassam, Saleem; Canada, Sallie; Cruz-Flores, Salvador; Mohamed, Samaa; Ly, Samantha; El Kaffas, Sameh; Massalha, Samia; Setty, Sampoornima; Nwosu, Samuel; Seth, Sandeep; Singh, Sandeep; Niehe, Sander R; Rivest, Sandra M; Zier, Sandra S; Ahoud, Sandra; Carr, Sandy; Ganapathi, Sanjay; Shetty, Sanjay; Sharma, Sanjeev; Jimenez, Santa; Satheesh, Santhosh; Garcia, Santiago A; Fernandez, Sara; Karlsson, Sara; Salkind, Sara; Temiyasathit, Sara; Medina Rodriguez, Sarah; Beaudry, Sarah; Hadjih, Sarah; Williams, Sarah; Zahrani, Sarah; Ralhan, Sarju; Hinic, Sasa; Kedev, Sasko; Singh, Satinder; Yasuda, Satoshi; Manjunath, Satvic Cholenahally; Lee, Sau; Kaczkowski, Scott M; Kinlay, Scott; Hayes, Sean W; Sobczak, Sebastian; Asier, Senait; Sayganov, Sergey A; Sokol, Seth I; Pandie, Shaheen; Yahaya, Shaiful Azmi; Mehta, Shamir; Nie, Shao-Ping; Chandra, Sharad; Islam, Sharder; Tai, Sharon; Karwa, Sheetal Rupesh; Ussery, Sheri; Bajaj, Sheromani; Crook, Sherron C; Nishimura, Shigeyuki; Nakano, Shintaro; Heydari, Shirin; Choudhary, Shiv Kumar; Patel, Shivali; Ganesan, Shobana; Pandey, Shruti; Zhang, Shuyang; Hande, Shweta; Gadage, Siddharth; Tan, Sik-Yin V; Zottis Poletti, Silvia; Riera, Silvia; Valbuena, Silvia; Walsh, Simon; Maspoli, Simona; Savaris, Simone; Feng, Si-Ting; Cho, So Yang; Yakubov, Solomon; Zhu, Songlin; Wang, Songtao; Guerrero, Sonia; Gupta, Sonika; Salinger Martinovic, Sonja; Brons, Sonya; Brener, Sorin; Gurunathan, Sothinathan; Saba, Souheil; Nayak, Soundarya; Reddy, Sowjanya; Potluri, Srinivasa; Sudarshan, Sriram; Kuanprasert, Srun; Van Oosterhout, Stacie; Lerakis, Stamatios; Cobos, Stanley E; Bertog, Stefan C; Simović, Stefan M; Weikl, Stefan; Di Marco, Stefano; Provasoli, Stefano; Tirado, Stephanie A; Boer, Stephanie C; Lane, Stephanie M; Ferket, Stephanie; Kelly, Stephanie; Wasmiller, Stephanie; McKellar, Stephen H; Hoole, Stephen P; Fremes, Stephen; Preston, Stephen; Leung, Steve; Fein, Steven A; Lindsay, Steven J; Sedlis, Steven P; Giovannone, Steven; Michael, Steven; Weitz, Steven; van Vugt, Stijn; Banerjee, Subhash; Naik, Sudhir; Hosino, Suellen; Desire, Sukie; Yamwong, Sukit; Thambar, Suku T; Mookherjee, Sulagna; Singh, Suman; Mishra, Sundeep; Verma, Sunil Kumar; Kulthawong, Supap; Khwakhong, Supatchara; Naik, Surendra; Babu, Suresh; Woragidpoonpol, Surin; Narayanappa, Suryaprakash; Derbyshire, Susan; Gent, Susan; Mathus, Susan; Milbrandt, Susan; Moore, Susan; Regan, Susan; Stinson, Susan; Webber, Susan; Silva, Susana; Stevens, Susanna; Gruensfelder, Susanne; Aramcharoen, Suthara; Kolhe, Suvarna; Tavares, Suzana; Arnold, Suzanne; Welsh, Suzanne; Apostolovic, Svetlana; Kunhunny, Swapna; Hung, Ta-Chuan; Zappernick, Taissa; Sharir, Tali; Silva, Talita; Soares, Tamara Colaiácovo; Pillay, Tapan Umesh; Mittal, Tarun K; Trifonova, Tatiana; Duarte, Tauane Bello; Huk, Tauqir; Dutoiu, Téodora; Chua, Terrance; Weyand, Terry; Charles, Thabitha; Kofidis, Theodoros; McCreary, Theresa; Lefevre, Thierry; Arumairajah, Thippeekaa; Tepsuwan, Thitipong; Mulhearn, Thomas J; Meyer, Thomas M; Rocco, Thomas P; Downes, Thomas R; Crain, Thomas; Haldis, Thomas; Mathew, Thomas; Redick, Thomas; Devi, Thounaojam Indira; Nageh, Thuraia; Cauthren, Tia; Silva, Tiago; Little, Tiffany; Andric, Tijana; Harding, Tina; Lau, Titus; Formisano, Tiziana; Moccetti, Tiziano; Ciurus, Tomasz; Mazurek, Tomasz; Tarchalski, Tomasz; Nagai, Toshiyuki; Tran, Tri; Youn, Tricia; Tucker, Trish; Milner, Trudie; Bose, Tuhina; Kotecha, Tushar; Sechtem, Udo; Valeti, Uma S; Cucchini, Umberto; Badami, Umesh; Kaul, Upendra; Bahl, V K; Narain, V S; Casali, Valentina; Godoy, Valeria; Robesyn, Valerie; Priya, Vamshi P; Yadav, Vandana; McKinney, Vera; De Lenges, Veronica; Tinnirello, Veronica; Miro, Vicente; Navarro, Victor; Gumerova, Victoria; Hernandez, Victoria; Seeratan, Vidya; Kumar, Vijay; Kozulin, Vikentiy Y; Bulkley, Viktoria; Veiga, Vilmar Jr; Setang, Vincent; Vineeth, C P; Pubull Nuñez, Virginai; Fernández-Figares, Virginia; Gomes, Vitor; Gabriel, Viviana; Dos Santos, Viviane; Almeida, Viviane; Iliescu, Vlad A; Mudrenovic, Vladan; Dzavik, Vladimir; Giga, Vojislav L; Mogrovejo, Walter Enrique; Chan, Wan Xian; Marfori, Wanda C; Parker, Wanda; Mekara, Warangkana; Nona, Wassim; Old, Wayne; Pennachi, Wayne; Nawarawong, Weerachai; Chen, Wei; Su, Wei; Xing, Weibing; Lan, Wei-Ren; Crawford, Wenda; Stewart, Wendy L; Drewes, Wendy; Lin, Wenhua; Abernethy, William B; Salerno, William D; Fearon, William F; Vergoni, William; Weintraub, William; Sia, Winnie C; Musial, Wlodzimierz J; Flores-Ríos, Xacobe; Garcia-Moll Marimon, Xavier; Su, Xi; Ma, Xiang; Gu, Xiangqiong; Wang, Xiao; Li, Xiaomei; Yao, Xiaowei; Fu, Xin; Su, Xin; Zeng, Xin; Yang, Xinchun; Li, Xiuhong; Fang, Xuehua; Wang, Xutong; Geng, Yaming; Yan, Yan; Pépin-Dubois, Yanek; Wang, Yanfu; Wang, Yang; Tian, Yanmeng; Huang, Yaping; Han, Yechen; Zambrano, Yesenia; Yang, Yi-Hsuan; Sia, Ying Tung; Yang, Yining; Ma, Yitong; Peralta, Yolayfi; Wu, Yongjian; Kunwu, Yu; Zhao, Yu; Peng, Yudong; Lin, Yueh-Hung; Zhao, Yulan; Dong, Yumei; Zhao, Yunhai; Wannasopha, Yutthaphan; Taul, Yvonne; Sahul, Zakir; Kudzoeva, Zalina; Kalarus, Zbigniew; Markovic, Zeljko Z; Huang, Zhen; Ji, Zheng; Liu, Zhenyu; Yue, Zhou; Zhang, Zhulin; Li, Zhuxi; Singh Meharwal, Zile; Bai, Ziliang; Yu, Zixiang; Huda, Zohra; Davidovits, Zoltan
BACKGROUND:Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS:We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS:Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS:Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).
PMID: 32227755
ISSN: 1533-4406
CID: 5451242
Journal of the American College of Cardiology. 2020:Conference:(ACC).DOI: 10.1016/S0735-2D1097-252820-252932843-2D6

INVESTIGATION OF CIRCULATING PCSK9, SYSTEMICALLY ALTERED PATHWAYS AND IMPAIRED VASCULAR HEALTH IN PSORIASIS [Meeting Abstract]

Grattan, R; Garshick, M S; Barrett, T; Tawil, M; Fisher, E; Krueger, J; Berger, J
Background Psoriasis is an inflammatory disease of the skin associated with heightened cardiovascular (CV) disease. Serum levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) associates with future CV risk and vascular dysfunction. We aimed to identify the relationship between pro-inflammatory pathways, circulating PCSK9, and vascular health in psoriasis. Methods Whole blood transcriptomics and serum proteomics was performed in 20 patients with psoriasis (mean age 42 +/- 14 years, 55% male, psoriasis area and severity index [PASI] 5 [3 - 11]) and 15 controls (mean age 41 +/- 14 years, 53% male) recruited into a clinical trial to assess vascular health in psoriasis (NCT03228017). Vascular health was assessed through flow mediated dilatation (FMD) and harvesting and analysis of brachial vein endothelial cells. Results Circulating PCSK9 was found to be 1.13-fold higher in psoriasis compared to controls (p=0.02) despite no difference in LDL-C (108 +/- 38 mg/dl vs. 90 +/- 25 mg/dl, respectively p=0.31). Circulating PCSK9 was correlated with psoriasis area severity index (PASI score, r=0.43, p=0.04) even after adjustment for age, gender, BMI and LDL-C (beta=0.02, p=0.03). Integration of the whole blood transcriptome yielded 322 transcripts which correlated with circulating PCSK9 (FDR<0.05). Network analysis of these transcripts highlighted interferon signaling (p=7.2x10-6), a known pathogenic process in psoriasis, as a key regulator of PCSK9. Finally, circulating PCSK9 positively correlated with brachial vein endothelial expression of the pro-inflammatory transcripts CXCL10 (r=0.69, p<0.001), ICAM1 (r=0.49, p=0.02) and IL1beta (r=0.38, p<0.01) and inversely correlated with the functional measure of endothelial health, FMD (r=-0.52, p=0.03). Conclusion Circulating PCSK9 is elevated in psoriasis and associated with impaired vascular health. Analysis of the relationship between PCSK9 and systemic pathways revealed prominent interactions between PCSK9 and interferon signaling. Further research to better characterize these transcriptome and proteome variations and how it impacts vascular health in psoriasis may help elucidate new targets for therapeutic interventions.
Copyright
EMBASE:2005039249
ISSN: 1558-3597
CID: 4381112
Journal of the American College of Cardiology. 2020:Conference:(ACC).DOI:

CHRONIC KIDNEY DISEASE IN HEART FAILURE PATIENTS UNDERGOING NON-CARDIAC SURGERY [Meeting Abstract]

Li, B; Wilcox, T; Smilowitz, N R; Newman, J; Berger, J
Background Heart failure (HF) and chronic kidney disease (CKD) commonly co-exist, and are associated with adverse postoperative cardiovascular outcomes. The impact of CKD in HF patients undergoing noncardiac surgery is uncertain. Methods Patients with HF undergoing non-cardiac surgery were identified from the National Surgical Quality Improvement Program between 2009-2015. Patients were classified into 5 groups based on estimated glomerular filtration rate (eGFR) and requirement of dialysis and were followed prospectively for the primary outcome of death and major adverse cardiovascular events (MACE; a composite of death, myocardial infarction (MI), and stroke) within 30-days post-operatively. Multivariable logistic regression models adjusted for age, sex, race, surgery type, and clinical history and surgery type were generated to estimate the association between CKD stage and outcomes. Results Among 27,612 HF patients undergoing surgery, 65.1% had CKD (19.7% with eGFR 45-60, 20.3% eGFR 30-45, and 25.1% eGFR < 30 with or without dialysis). The incidence of postoperative death and MACE increased with worsening CKD (Table). After multivariable adjustment, eGFR <60 was associated with increased odds of MI and cardiac arrest and eGFR <45 was associated with postoperative mortality. No association was observed between CKD and stroke. Conclusion Among HF patients, the presence of CKD is common and is associated with increased risk for postoperative mortality and MACE. [Figure presented]
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EMBASE:2005039289
ISSN: 0735-1097
CID: 4367642
Vascular medicine. 2020.DOI: 10.1177/1358863X19898253

Heparin-induced thrombocytopenia (HIT): Review of incidence, diagnosis, and management

Hogan, Marie; Berger, Jeffrey S
Heparin-induced thrombocytopenia (HIT) is a life and limb-threatening complication of heparin exposure. Here, we review the pathogenesis, incidence, diagnosis, and management of HIT. The first step in thwarting devastating complications from this entity is to maintain a high index of clinical suspicion, followed by an accurate clinical scoring assessment using the 4Ts. Next, appropriate stepwise laboratory testing must be undertaken in order to rule out HIT or establish the diagnosis. In the interim, all heparin must be stopped immediately, and the patient administered alternative anticoagulation. Here we review alternative anticoagulation choice, therapy alternatives in the difficult-to-manage patient with HIT, and the problem of overdiagnosis.
PMID: 32195628
ISSN: 1477-0377
CID: 4353772