tbuckley/cabot-search huggingface dataset:
NICE sets cap on drugs costing more than £20m
Authors: Nigel Hawkes
Journal: BMJ (2017)

The Association of the British Pharmaceutical Industry has accused the government of breaking its promise to speed up the introduction of cost effective drugs into the NHS.

The association said that proposals by the National Institute for Health and Care Excellence (NICE) and NHS England to refuse to pay for any new drug that will cost more than £20m (€23m; $24m) a year was a breach of a pledge made in the Conservative Party’s election manifesto in 2015.

The decision means that new drugs would not only have to meet NICE’s threshold of cost effectiveness—set at about £20 000 to £30 000 …
Long-Term Experience with Hypomethylating Agents in Patients with Chronic Myelomonocytic Leukemia
Authors: Ana Alfonso Pierola, Guillermo Montalban-Bravo, Koichi Takahashi, Elias J. Jabbour, Tapan M. Kadia, Farhad Ravandi, Jorge E. Cortes, Courtney D. DiNardo, Naval G. Daver, Gautam Borthakur, Naveen Pemmaraju, Marina Konopleva, Carlos E. Bueso-Ramos, Sherry Pierce, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2016)
PATIENTS WITH NON ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION UTILIZING MEDICARE/MEDICAID HAVE LOWER ADJUSTED ODDS OF IN-HOSPITAL MORTALITY: A NATIONWIDE ANALYSIS
Authors: Farid Gholitabar, Carlos Gongora, Shawn Lee, Alejandro Lemor, Abel Casso Dominguez, Eyal Herzog
Journal: Journal of the American College of Cardiology (2017)
DIVERSE PERSPECTIVES AND TRAINING PATHS IN CARDIOLOGY: AN ANALYSIS OF AUTHORSHIP IN THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Authors: Barbara Anna Danek, Aris Karatasakis, Judit Karacsonyi, Phuong-Khanh Nguyen-Trong, Erica Resendes, Bavana Rangan, Michele Roesle, Amy Atwell, Paul Sorajja, Houman Khalili, Shuaib Abdullah, Subhash Banerjee, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2017)
Phase II trial of RO4929097 Notch gamma-secretase inhibitor in metastatic melanoma: SWOG S0933.
Authors: Kim Allyson Margolin, James Moon, Bruce G. Redman, Tarek Chidiac, Megan Othus, Antoni Ribas, Lawrence E. Flaherty, Vernon K. Sondak, Thomas Gajewski
Journal: Journal of Clinical Oncology (2012)

8525 Background: The Notch pathway regulates expression of genes for cell cycle, tissue-specific differentiation, and vasculogenesis. Notch target genes affect melanomagenesis, and Notch levels can influence stemlike versus differentiated tumor cells. Gamma-secretase, which activates intracellular Notch, can be inhibited to kill melanoma cells. We designed this trial to test RO4929097 in pts with melanoma and its effects on T lymphocytes and tumor gene expression. Methods: To assess 6-month progression-free survival (PFS) and 1-year overall survival (OS) in advanced, untreated melanoma patients (pts), a 2-stage accrual design was used. Correlative studies: markers of Notch pathway activation in archived or fresh tumor and T cell functional assays pre-treatment (Rx) and at week 3. Rx dose was 20 mg orally on 3 consecutive days, weekly. Results: 33 pts were Rx’d in stage 1 (median age 61 [range 32-85]; 70% male; 42% elevated LDH; 30% unknown primary; 24% bone mets; 36% liver; 55% lung; 55% lymph node, skin or soft tissue). The clinical outcomes did not meet criteria for stage 2 accrual. One pt had a confirmed PR of 7 months’ (mo) duration. The median PFS was 1.4 mo, [95% confidence interval, c.i. 1.3-2.7], the 6-mo PFS was 11% [95% c.i 3%-33%], and the 1-year OS was 45% [95% c.i. 23%-90%]. Treatment was well-tolerated with no grade (gr) 4-5 tox. The most common gr 2 drug tox were fatigue and nausea in 4 patients (12%) each, and only 4 of 7 gr 3 tox were considered drug-related (1 increased ALT, 1 QTc prolongation, 1 bradycardia, 1 lymphopenia). Pre- and week 3 on-Rx peripheral T cell samples assayed for IL-2 (23 pts) and IFN-γ (22 pts) secretion to Staphylococcal enterotoxin A showed no significant change, in contrast to in vitro gamma-secretase inhibitors which blocked T cell activation. Pre- and on-Rx tumor biopsies in one pt showed no decrease in the Notch target Hey1. Conclusions: RO4929097 at this dose and schedule has limited activity in molecularly-unselected pts with melanoma. Lack of effect on T cell function and tumor Hey1 expression suggests that sustained target inhibition might not have been achieved. Supported in part by PHS Cooperative Agreements, NCI, DHHS CA32102 and CA38926. ClinicalTrials.gov identifier: NCT01120275.
Histology of Lymphomas with t(3;14)(q27;q32) Correlates with the Molecular Anatomy of the Translocation.
Authors: Philippe Ruminy, Fabrice Jardin, Jean-Michel Picquenot, Philippe Gaulard, Françoise Parmentier, Gérard Buchonnet, Claire Maisonneuve, Hervé Tilly, Christian Bastard
Journal: Blood (2005)
The effect of ethnicity on presentation, pattern of metastasis, and survival in gastric adenocarcinoma at a single center
Authors: J. F. Tseng, P. F. Mansfield, B. W. Feig, P. W. Pisters, J. A. Ajani, J. C. Yao
Journal: Journal of Clinical Oncology (2004)

4016 Background: The effect of race/ethnicity in gastric cancer remains incompletely delineated. Methods: 1920 patients with gastric adenocarcinoma who were treated at MD Anderson Cancer Center from 1985–1999 served as the study cohort. Median survival duration was estimated by the Kaplan-Meier method. Cumulative survival was compared using the log-rank test. Self-identified race, AJCC stage, WHO histology, gastric subsite, age, and sex were entered into a Cox proportional hazards model for multivariate survival analysis. Results: 1352 patients (70%) were white/Caucasian; 301 (16%) were Latino; 163 (8%) were African-American; 81 (4%) were Asian; 19 (2%) were unknown. 63% were men. Gastric cancer location and stage varied by race (p<0.0005); Asians were more likely to have mid- or distal gastric involvement (62%, vs 42% for African-Americans, 18% for Latinos, 13% for whites), and less likely to have metastases (p=0.007) (AJCC Stage IV: 37% of Asians, 68% of African-Americans, 59% of Latinos, 56% of whites). Of patients who had their first site of metastasis to either liver or peritoneal cavity (n=808), Asians were more likely than other groups to have peritoneal rather than liver metastasis (p=0.001). White, Latino, and African-American patients had unadjusted median survivals less than half that of Asians (12.0, 10.8, and 10.5 months vs 26.7, respectively). After adjusting for demographic and tumor characteristics, compared to whites, Latinos had a similar risk of death (HR 1.08, 95% CI 0.91–1.28), while African-Americans had an increased risk (HR 1.29, 95% CI 1.04–1.59, p=0.021) and Asians had a decreased risk of death (HR 0.70, 95% CI 0.50–0.96, p=0.028). Conclusions: We report a large single-center experience with gastric adenocarcinoma in an ethnically diverse patient population. After multivariable analysis, Latinos have equivalent survival to whites, whereas African-Americans demonstrate decreased and Asian have increased survival compared to all other races. These differences were independent of stage, histology, tumor location, age, and gender. Factors contributing to these differences warrant further investigation. No significant financial relationships to disclose.
The use of immunosuppression in autoimmune hepatitis: A current literature review
Authors: Angela Cropley, Martin Weltman
Journal: Clinical and Molecular Hepatology (2017)

Autoimmune hepatitis (AIH) is an organ specific autoimmune condition which can manifest at any age of life. The heterogeneous nature of this condition means that great variation can be seen in severity, progression of disease and response to treatment within this patient group. Since the 1980s prednisolone and azathioprine have been used for induction and remission of the disease and remain the mainstay of treatment. Other immunosuppressive agents have been employed in difficult to treat cases. While there is less published data regarding these agents compared with the conventional treatments of steroid and azathioprine, there is mounting evidence to support the use of mycophenolate mofetil as a second-line agent. The calcineurin inhibitors, though less studied, additionally show promise. More data is needed on the use of biological agents in refractory disease. This review focuses on our centre's approach to treatment of AIH in the context of a contemporary review of the literature.
The Role of Pancreatic Preproglucagon in Glucose Homeostasis in Mice
Authors: Adam P. Chambers, Joyce E. Sorrell, April Haller, Karen Roelofs, Chelsea R. Hutch, Ki-Suk Kim, Ruth Gutierrez-Aguilar, Bailing Li, Daniel J. Drucker, David A. D’Alessio, Randy J. Seeley, Darleen A. Sandoval
Journal: Cell Metabolism (2017)
DOES FRAILTY ALTER THE BENEFITS OF ORAL ANTICOAGULATION IN PATIENTS WITH ATRIAL FIBRILLATION?
Authors: Malini Madhavan, DaJuanicia Simon, Jonathan Piccini, Jack Ansell, Gregg Fonarow, Alan S. Go, Elaine Hylek, Peter Kowey, Kenneth Mahaffey, Laine Thomas, Eric Peterson, Bernard Gersh
Journal: Journal of the American College of Cardiology (2017)
Retrospective evaluation of premenopausal hormone-sensitive breast cancer patients treated with adjuvant gonadotropin-releasing hormone analogue.
Authors: Ayse Demirci, Necati Alkis, Faysal Dane, Dogan Yazilitas, Ayse Durnali, Mevlude Inanc, Melike Ozcelik, Tulay Akman, Omer Kamil Yazici, Muhammet Ali Kaplan, Arife Ulas, Oznur Bal, Ozlem Sonmez, Saadet Tokluoglu, Yusuf Gunaydin, Gamze Gokoz Dogu, Ozgur Tanriverdi, Umut Demirci, Alper Sevinc, Ibrahim Turker
Journal: Journal of Clinical Oncology (2014)

e11542 Background: Breast cancer is the most common cancer in women. Approximately 60% of breast cancer are hormone receptor positive. The goal of this study is to evaluate the possible factors affecting the survival of patients treated with gonadotropin-releasing hormone (GnRH). Methods: Demographic characteristics, treatment modalities, overall survival and the possible factors affecting the survival a total of 539 premenoposal breast cancer patients from 16 different centers in Turkey analysed retrospectively. Results: Median age was 36±6.3 (19-53). The median tumour size was 2.5±1.8 (0.5-13) cm. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) positivity rates were 92.0%, 90.4% 31.4% respectively. Histology of the tumors were as follows; invasive ductal carcinoma in 85.3%, invasive lobular carcinoma in 4.6%, mixed in 4.6%, and other subtypes in 5.3%. T staging were T1, T2, T3, T4 in 25.8%, 49.9%, 13.4%, 1,7% respectively. Lymph node involvement was in 61.1%. Neoadjuvant therapy, adjuvant chemotherapy and radiation therapy were applied in 8.5%, 88.9% and 81.3% of patients, respectively. Median duration of GnRH analogue use was 23.0±13.8 (1-87) months. Patients were divided into 3 groups according to duration of GnRH analogues use. The time was shorter than 24 months, equal to 24 months, and longer than 24 months in the first group (n=268, 49.7%) , second group (n=88, 16.3%) , and the third group (n=162, 30.1%) respectively. Median follow up was 33.5 months (1-188). Median DFS was 126.0±11.6 (103-148) months. According to the groups median DFS were 104.0±31.2 (42.7-165) and 116.0±8.4 (99-132) months in first and third group. But median DFS couldn’t be calculated in the second group because of low recurrence numbers (log rank, p<0,005). There was no difference between groups according to the OS (log rank, p=0.20). Median OS was reached only in the second group (175.0±66.7 [44-305]). Conclusions: In this study we can not find the optimal duration of adjuvant GnRH use in premenopausal HR positive breast cancer patients. Additional prospective randomised studies are needed to clarify theese results.
IMPACT OF RENIN-ANGIOTENSIN SYSTEM BLOCKERS ON LONG TERM SURVIVAL FOLLOWING ISOLATED AORTIC VALVE REPLACEMENT FOR AORTIC STENOSIS
Authors: Victor Aboyans, Julien Magne, Barthelemy Guinot, Antoine Bourgeois, Alessandro Piccardo, Alexandre Le Guyader, Dania Mohty
Journal: Journal of the American College of Cardiology (2017)
Abstract A17: Probing a translational switch involved in tumor angiogenesis
Authors: Maya Ramachandran, Somdeb Mitra, Ruben L. Gonzalez
Journal: Cancer Research (2017)

Abstract As a tumor proliferates, it rapidly outgrows its blood supply, creating an oxygen-starved environment. Low oxygenation (hypoxia) suppresses the canonical biochemical pathway through which the translation of messenger RNAs (mRNAs) into proteins by the ribosome is typically initiated. Despite shutting down this general mechanism for initiating protein synthesis, the tumor can continue to initiate translation of a subset of mRNAs that are involved in angiogenesis and tumor survival. To explain this observation, it has been proposed that, in addition to the eukaryotic mRNA-specific 7-methyl guanosine cap at the 5' end, these pro-angiogenic mRNAs, of which Fibroblast Growth Factor-9 (FGF9) and Hypoxia Inducible Factor 1α (HIF1α) are prototypical members, contain highly stable structures in their 5' untranslated regions. These structures, also referred to as Cap Independent Translation Enhancers (CITEs), form part of a switch that activates a non-canonical pathway for initiating translation, presumably by binding directly to eukaryotic initiation factor 4G (eIF4G), thereby recruiting ribosomes in a manner distinct from the canonical 5' cap-dependent mechanism. To test this hypothesis, here we report the binding affinities of pro-angiogenic mRNAs, as well as control mRNAs lacking CITEs, to eIF4G as a measure of their ability to initiate translation in the hypoxic environment of a tumor. Understanding the dynamics of eIF4G-CITE interactions can inform the design and development of novel angiogenesis inhibitors that function by targeting these interactions. Citation Format: Maya Ramachandran, Somdeb Mitra, Ruben L. Gonzalez, Jr. Probing a translational switch involved in tumor angiogenesis. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr A17.
ARE THE CARDIOVASCULAR RISK REDUCTIONS SEEN WITH EMPAGLIFLOZIN IN THE EMPA-REG OUTCOME TRIAL EXPLAINED BY CONVENTIONAL CARDIOVASCULAR RISK FACTORS?
Authors: David H. Fitchett, Ruth L. Coleman, Alistair Gray, Uli C. Broedl, Jyothis George, Hans-Juergen Woerle, Bernard Zinman, Rury R. Holman
Journal: Journal of the American College of Cardiology (2017)
RELATIONS BETWEEN FIBROSIS-LINKED MICRORNAS (MIR-21, MIR-26, MIR-29, MIR-30 AND MIR-133A) AND RIGHT VENTRICULAR MORPHOLOGY AND FUNCTION IN DILATED CARDIOMYOPATHY
Authors: Pawel Rubis, Justyna Totoń-Żurańska, Sylwia Wisniowska-Smialek, Katarzyna Holcman, Paweł Wołkow, Ewa Wypasek, Joanna Natorska, Lucyna Rudnicka-Sosin, Agnieszka Pawlak, Artur Kozanecki, Piotr Podolec
Journal: Journal of the American College of Cardiology (2017)
IMPROVEMENT IN COST AND EFFICIENCY IN ELECTROPHYSIOLOGY LABORATORY BY CARDIAC COMPUTED TOMOGRAPHY TO EXCLUDE LEFT ATRIAL APPENDAGE THROMBUS PRIOR TO ATRIAL FIBRILLATION ABLATION
Authors: Ali Sheikh, Zaid Said, Mohamed Abdel-Aal Ahmed, Wassim Mosleh, Michael Wilson, Hiroko Beck, Chee Kim, Umesh Sharma
Journal: Journal of the American College of Cardiology (2017)
Onapristone (ONA) in progesterone receptor (PR)-expressing tumors: Efficacy and biomarker results of a dose-escalation phase 1 study.
Authors: Paul H. Cottu, Antoine Italiano, Andrea Varga, Mario Campone, Alexandra Leary, Anne Floquet, Dominique Berton-Rigaud, Marie-Paule Sablin, Anne Lesoin, Catherine Lhomme, Alice Susannah Bexon, Erard M. Gilles, David Jackson, Joseph Bisaha, Alexander Zukiwski, Jacques Bosq, Jacques Bonneterre
Journal: Journal of Clinical Oncology (2015)

5593 Background: ONA is a type I PR antagonist, which prevents PR-induced DNA transcription. Immediate release (IR) 100 mg ONA was active in multiple preclinical models and in patients (pts) with breast cancer (BC). We conducted a phase 1 study of extended release (ER) ONA to (i) determine a recommended dose and (ii) explore the role of transcriptionally-activated PR (APR), detected as an aggregated subnuclear distribution pattern, as a predictive immunohistochemical (IHC) biomarker. Methods: An open-label, multicenter, randomized, parallel-group, phase 1 study (target n=48; NCT02052128) included female pts ≥18 years with PRpostumors. APR analysis was performed on archival tumor tissue. Pts were randomized to 5 cohorts of ER ONA tablets 10-50 mg BID, or IR 100 mg QD until progressive disease or intolerability. This abstract reports the APR IHC analysis and clinical benefit (PR/SD≥24 wks). Results: Phase 1 is complete (n=52). Tumors (n) were: endometrial carcinoma (EC) 13; breast cancer (BC) 20; ovarian cancer (OC) 13; other 6. Median age was 66 (37-85). No dose limiting toxicity was observed with only transient liver function test elevation, mostly related to liver metastases. PRpos/APRpostumors (n/n) were: EC 11/6, BC 8/3, OC 5/1, other 2/0 and 8 pts (6 BC) had missing/non evaluable IHC. Median therapy duration was 8 wks (range 2-44), and 8 pts had clinical benefit ≥24 weeks (see Table). Conclusions: Clinical benefit was seen in heavily-pretreated pts with EC, OC and BC. Data support ongoing ONA development at 50mg ER BID in APRpos uterine endometrioid cancer with clinical validation of the APR diagnostic. Meanwhile, further development of APR IHC is needed in OC and BC. Clinical trial information: NCT02052128.Response and stable disease for ≥24 weeks. Tumor type PR % retest APR status #Prior Rx Dur-n Prior Rx months Mets Dose Response % change STL Dur-n (wks) Serous OC 0 Neg 3 8 LN 10 PR -52 40 Serous OC 0 Neg 4 6.5 LN 50 SD -7 34 Granulosa OC A: 20 B: 20 Neg 2 5 Liver, peritoneal 40 SD -24 24 Granulosa OC A: 80 B: 70 Neg 4 6 Liver, peritoneal spleen 30 SD +5 32 EC A: 80 B: 60 Pos 2 3 Lung, bone 30 SD -13 30+ EC A: 60 B: 70 Pos 2 6.5 Pelvis, lung 20 SD +5 32 BC A: 50 B: 50 Neg 2 +3H 11 Liver, bone 50 SD -7 32+ BC A: 60 B: 40 Pos 2 +3H 6.5 Liver, bone 40 SD -10 24
MAOA-Dependent Activation of Shh-IL6-RANKL Signaling Network Promotes Prostate Cancer Metastasis by Engaging Tumor-Stromal Cell Interactions
Authors: Jason Boyang Wu, Lijuan Yin, Changhong Shi, Qinlong Li, Peng Duan, Jen-Ming Huang, Chunyan Liu, Fubo Wang, Michael Lewis, Yang Wang, Tzu-Ping Lin, Chin-Chen Pan, Edwin M. Posadas, Haiyen E. Zhau, Leland W.K. Chung
Journal: Cancer Cell (2017)
WOMEN WHO EXPERIENCE MYOCARDIAL INFARCTION AT A YOUNG AGE HAVE WORSE SURVIVAL COMPARED WITH MEN
Authors: Bradley Collins, Avinainder Singh, Arman Qamar, Sanjay Divakaran, Julio Baez, Josh Klein, Jon Hainer, Petr Jarolim, Ravi Shah, Jorge Plutzky, Donna Polk, Khurram Nasir, Marcelo Di Carli, Deepak Bhatt, Ron Blankstein
Journal: Journal of the American College of Cardiology (2017)
PERFORMANCE OF J-CTO AND PROGRESS CTO SCORES IN PREDICTING ANGIOGRAPHIC SUCCESS AND LONG-TERM CLINICAL OUTCOMES OF PERCUTANEOUS CORONARY INTERVENTIONS FOR CHRONIC TOTAL OCCLUSIONS
Authors: Farshad Forouzandeh, Jon Suh, Eric Stahl, Suegene Lee, Yi-An Ko, Udit Joshi, Nitin Sabharwal, Rounak Gandhi, Zakaria Almuwaqqat, Sung Ahn, Bill Gogas, Gregory Robertson, Wissam Jaber, Dimitrios Karmpaliotis, William Nicholson, Habib Samady
Journal: Journal of the American College of Cardiology (2017)
Safety results of the enzalutamide expanded access program in the United States and Canada for patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel.
Authors: Anthony M. Joshua, Neal D. Shore, Fred Saad, Kim N. Chi, Carl A. Olsson, Urban Emmenegger, Mark C. Scholz, William R. Berry, Som Mukherjee, Eric Winquist, Naomi B. Haas, Nahla Hasabou, Carl Dmuchowski, Frank Perabo, Mohammad Hirmand, Margaret A. Foley, Dana E. Rathkopf
Journal: Journal of Clinical Oncology (2014)

5051 Background: In the Phase 3 AFFIRM trial, the androgen receptor inhibitor enzalutamide improved overall survival compared with placebo in patients (pts) with mCRPC who had received prior docetaxel. The aim of this open-label single-arm study was to monitor safety and provide access to enzalutamide for mCRPC pts pending marketing approval in the U.S. and Canada. Methods: 507 pts with mCRPC were treated at 54 sites. Pts received enzalutamide 160 mg/d in the study until disease progression, intolerable adverse event (AE), or commercial availability. AEs, serious AEs (SAEs), vital signs, and laboratory measurements were assessed on day 1, wk 4 and 12, and every 12 wks thereafter. No efficacy data were collected. Results: Median age was 71 yr (range 43-97). Baseline ECOG PS was 0, 1 and 2 in 27.8%, 56.1%, and 15.9% of pts, respectively. Prior treatments for prostate cancer included abiraterone (76.0%), and cabazitaxel (28.6%); 24.8% of pts received both prior abiraterone and cabazitaxel. Median enzalutamide treatment duration in the study was 2.6 mo (range 0.03-9.07); data following transition to commercial drug was not collected. Common AEs (≥10%) included fatigue (39.1%), nausea (22.7%), anorexia (14.8%), anemia (11.8%), peripheral edema (11.4%), back pain (10.3%), vomiting (10.3%), and arthralgia (10.1%). SAEs reported in ≥1% of pts were disease progression (7.9%), pneumonia (2.0%), asthenia (1.8%), anemia (1.6%), and back pain (1.4%). Drug-related AEs leading to permanent discontinuation occurred in 3.7% of pts. Grade ≥3 drug-related AEs were reported in 14.2 % of pts and drug-related AEs leading to death occurred in 4 pts: 1 cerebrovascular accident, 2 myocardial infarctions and 1 death not otherwise specified. Seizure was reported in 4 (0.8%) pts, of whom 3 had brain metastases. Conclusions: In this expanded access population of pts with progressive mCRPC who had previously received docetaxel, enzalutamide was well tolerated. The safety profile was consistent with that seen in the AFFIRM trial. Median treatment duration was shorter than in AFFIRM (2.6 vs 8.3 mo); duration on subsequent commercial drug was not collected. Clinical trial information: NCT01606982.
STRESS MYOCARDIAL PERFUSION IMAGING VERSUS EXERCISE TREADMILL TESTING: COMPARISON OF CLINICAL AND ECONOMIC OUTCOMES IN REAL-WORLD EMERGENCY DEPARTMENT SETTINGS
Authors: John J. Mahmarian, Manuel Cerqueira, Tanya Burton, Jerry Seare, Rita Kristy, Therese Kitt, James Spalding
Journal: Journal of the American College of Cardiology (2017)