Late-Breaking Clinical Trial Abstracts
2015 Late-Breaking Clinical Trial Abstracts
Heart Failure and Cardiomyopathies
Failure is Not an Option: New Drugs and Systems of Care
20102 A Randomized Trial of Liraglutide for High-Risk Heart Failure Patients With Reduced Ejection Fraction
Kenneth B Margulies1, Kevin J Anstrom2, Margaret M Redfield3, Michael M Givertz4, Guilherme H Oliveira5, Robert Cole6, Doug Mann7, David J Whellan8, Michael S Kiernan9, G. Michael Felker10, Steven E McNulty10, Monica R Shah11, Adrian F Hernandez10, Eugene Braunwald12, Thomas P Cappola1; 1Medicine (Cardiology), Univ of Pennsylvania, Philadelphia, PA, 2Duke Clinical Rsch Institute, Duke Univ, Philadelphia, PA, 3Medicine (Cardiology), Mayo Clinic, Rochester, MN, 4Medicine (Cardiology), Brigham and Women's Hosp, Boston, MA, 5Medicine (Cardiovascular Medicine), UH Case Med Cntr, Cleveland, OH, 6Medicine (Cardiology), Emory Univ, Atlanda, GA, 7Medicine (Cardiovascular), Washington Univ in St. Louis, St. Louis, MO, 8Medicine (Cardiology), Thomas Jefferson Univ, Philadelphia, PA, 9Medicine (Cardiology), Tufts Univ, Boston, MA, 10Duke Clinical Rsch Institute, Duke Univ, Durham, NC, 11Cardiovascular Sciences, National Heart Lung and Blood Institute, Bethesda, MD, 12Cardiovascular Medicine, Brigham and Women's Hosp, Boston, MA,
Background: The heart consumes more energy per gram than any other organ, and myocardial metabolic demands are further increased in the failing heart. As heart failure (HF) progresses, the myocardium develops defects in substrate utilization including reduced fatty acid utilization and insulin resistance that impair glucose uptake. Synthetic GLP-1 agonists improve insulin sensitivity and represent promising metabolic modulators for patients with HF. Methods: The Functional Impact of GLP-1 for Heart Failure Treatment (FIGHT) study is a randomized, double-blinded, placebo-controlled clinical trial in high-risk HF patients with reduced ejection fraction (LVEF ≤ 40%) and recent hospitalization. 300 subjects were randomized to treatment with either the GLP-1 agonist liraglutide or placebo delivered by daily SQ injection. FIGHT included patients with and without type-2 diabetes, and a randomized block design to assure equal allocation of diabetics and non-diabetics to the two treatment arms. The primary end point of FIGHT is a global rank endpoint in which all participants, regardless of treatment assignment, are ranked across three hierarchical groups: 1) time to death, 2) time to HF hospitalization, and 3) time-averaged proportional change in NT-proBNP (from baseline to 180 days). The principal secondary end points include change in cardiac structure and function (by echocardiography) from baseline to 180 days. Additional endpoints include functional status based on the six-minute walk distances at 30, 90, and 180 days, changes in symptoms, based on the KCCQ, from baseline to 180 days, and individual components of the primary endpoint at 30, 90 and 180 days after randomization. Results: Enrollment in FIGHT was completed in March 2015 and follow up and database finalization will be completed in September. Baseline characteristics of the 300 patients include (median (25th, 75th) or %): Age 61 years (51, 68); Female 21%; Black 38%; Ischemic heart disease 82%, Hypertension 79%; Diabetes 60%; NYHA II/III 29%/65%, and LVEF 23% (17, 27). Conclusion: FIGHT is the first multicenter trial of a GLP-1 receptor agonist in the treatment of high-risk HF with reduced ejection fraction and will determine if this intervention improves clinical status at 180 days.
Author Disclosures: K.B. Margulies: Consultant/Advisory Board; Modest; Merck, Sharp and Dohme; Pfizer, Inc. K.J. Anstrom: Research Grant; Modest; AstraZeneca. Consultant/ Advisory Board; Modest; Pfizer, Abbot Vascular, AstraZeneca. M.M. Redfield: Honoraria; Modest; Heart Failure Society of America. Consultant/Advisory Board; Modest; Novartis (unpaid). Other; Modest; Anexion (Royalties). M.M. Givertz: Research Grant; Modest; Bristol Myers Squibb, Merck, Portola. Research Grant; Significant; AstraZeneca, Glaxo Smith Kline. Consultant/Advisory Board; Modest; Amgen, AstraZeneca, Bayer, Bristol- Myers Squibb, Gilead, Glaxo Smith Kline, Janssen, Merck, Pluristem Therapeutics, Inc., Sensible. Consultant/Advisory Board; Significant; Novartis. G.H. Oliveira: Research Grant; Significant; Frankino-Dodero Foundation. Speakers Bureau; Modest; Amgen, Novartis. Consultant/Advisory Board; Modest; Abiomed. R. Cole: None. D. Mann: None. D.J. Whellan: Research Grant; Significant; ResMed, Poszen. M.S. Kiernan: None. G. Felker: Research Grant; Significant; Roche Diagnostics, Novartis, Amgen, Otsuka, Singulex. Consultant/ Advisory Board; Modest; Trevena, Merck, Celladon. Consultant/Advisory Board; Significant; Novartis, Amgen. S.E. McNulty: None. M.R. Shah: None. A.F. Hernandez: Consultant/ Advisory Board; Modest; Novartis, Janssen, Bristol-Myers Squibb. E. Braunwald: Research Grant; Significant; AstraZeneca. Consultant/Advisory Board; Modest; Genzyme, Amorcyte, Medicines Co., CardioRentis, Sanofi-Aventis. Other; Modest; Eli Lilly (Lectures), Daichi Sankyo (Lectures), Menarini International (Lectures), Medscape (Lectures), Bayer (Lectures). T.P. Cappola: Consultant/Advisory Board; Modest; Teva Pharmaceuticals, Novartis.
13362 Nitrate’s Effect on Activity Tolerance in Heart Failure With Preserved Ejection Fraction (NEAT-HFpEF)
Margaret M Redfield1, Kevin J Anstrom2, James A Levine3, Barry Borlaug1, Horng Chen1, Martin M LeWinter4, Susan M Joseph5, Sanjiv J Shah6, Marc J Semigran7, G M Felker8, Robert T Cole9, Gordon Reeves10, Ryan J Tedford11, Wilson Tang12, Steven E McNulty2, Eric J Velazquez2, Monica R Shah13, Eugene Braunwald14, NHLBI Heart Failure Clinical Rsch Network; 1Cardiovascular Disease, Mayo Clinic & Foundation, Rochester, MN, 2Outcomes, Duke Clinical Rsch Institute, Durham, NC, 3Cardiovascular Disease, Mayo Clinic & Foundation, Scottsdale, AZ, 4Div of Cardiology, Univ of Vermont Med Cntr, Burlington, VT, 5Div of Cardiology, Washington Univ Sch of Medicine, St. Louis, MO, 6Div of Cardiology, Northwestern Univ, Chicago, IL, 7Div of Cardiology, Massachusetts General Hosp, Boston, MA, 8Div of Cardiology, Duke Univ Med Cntr, Durham, NC, 9Div of Cardiology, Emory Univ, Atlanta, GA, 10Div of Cardiology, Thomas Jefferson Univ, Philadelphia, PA, 11Div of Cardiology, Johns Hopkins Univ Sch of Medicine, Baltimore, MD, 12Cardiovascular Disease, The Cleveland Clinic Foundation, Cleveland, OH, 13NHLBI, NIH, Bethesda, MD, 14Div of Cardiology, Brigham & Women's, Boston, MA,
Background: Exercise intolerance is a cardinal feature of heart failure (HF) with preserved ejection fraction (HFpEF) and perpetuates sedentary behavior, deconditioning and frailty. While nitrates are commonly prescribed for symptom relief in HFpEF, no study has tested their effect in HFpEF. Hypothesis: Isosorbide mononitrate (ISMN) will enhance activity tolerance in HFpEF and thus, daily activity as assessed by patient worn accelerometry devices (AXM). Methods: NEAT-HFpEF was a multi-center, randomized, double-blind, 12 wk crossover study of ambulatory HFpEF patients (n=110). Entry criteria included HF symptoms, EF ≥ 50% and objective clinical (HF hospitalization), biomarker (NT-proBNP) or echocardiographic evidence of HF. During each 6 wk phase of the crossover study, patients took no study drug for 2 weeks (Baseline/Washout), then 30 mg for one wk, 60 mg for one wk and 120 mg for two wks. The primary endpoint was average daily accelerometry units (ADAU) during 2 wks of 120 mg/day of ISMN versus placebo as assessed by hip worn, tri-axial AXM worn throughout the study. Secondary endpoints included alternate activity indices (hours active/day at 120 mg dose and ADAU during all doses (30-120 mg)), six minute walk distance (6MWD), quality of life (QOL) scores, NT-proBNP and dose response. Treatment effect (TE) analysis adjusted for phase, sequence, baseline values and random effect of each patient. Results: Baseline characteristics (median or %): Age (69 yrs), Female (57%), BMI (34.7 kg/m2), NYHA II (53%) or III (45%) symptoms, KCCQ QOL score (54), 6MWD (312 m).ISMN tended to decrease ADAU at the 120 mg dose (TE -381, p=0.06) and significantly decreased hours active/day during 120 mg (TE -0.3 hours, p=0.02) and ADAU during all doses, (TE -439, p=0.02). ADAU decreased progressively and significantly as the ISMN (but not placebo) dose increased. ISMN had no effect on 6MWD, QOL scores or NT-proBNP. Numerically more patients had side effects during ISMN. Conclusions: These findings do not support use of ISMN in HFpEF. Reduced activity during ISMN is of concern as decreased activity promotes frailty. Data on activity from patient worn devices provides unique, patient-centric information about the impact of HF therapies on patient’s lives.
Author Disclosures: M.M. Redfield: None. K.J. Anstrom: Research Grant; Significant; NIH. J.A. Levine: Research Grant; Modest; Boeing. Consultant/Advisory Board; Modest; Kersh Health Risk Management, Gentag, SP Health. B. Borlaug: Research Grant; Significant; Mast Therapeutics, Medtronic. Consultant/Advisory Board; Significant; Merck, Amgen, AstraZeneca. H. Chen: None. M.M. LeWinter: Research Grant; Significant; NIH. S.M. Joseph: None. S.J. Shah: Research Grant; Significant; NIH, Actelion. Consultant/Advisory Board; Modest; AstraZeneca, Bayer, Alnylam. Consultant/Advisory Board; Significant; Novartis. M.J. Semigran: Other Research Support; Significant; St. Jude Medical. Consultant/Advisory Board; Significant; Broadview, Novartis. G.M. Felker: Research Grant; Significant; NIH, Roche Diagnostics, Novartis, Amgen, Otsuka, Singulex. Consultant/Advisory Board; Modest; Trevena, Merck, Celladon, Medtronic. Consultant/Advisory Board; Significant; Novartis, Amgen. R.T. Cole: None. G. Reeves: Employment; Significant; Thomas Jefferson University. Other Research Support; Significant; ResMed Foundation, Thoratec. R.J. Tedford: Other; Significant; Merck. W. Tang: Research Grant; Significant; National Institutes of Health. S.E. McNulty: None. E.J. Velazquez: None. M.R. Shah: None. E. Braunwald: None.
16885 Oral sGC Stimulator Vericiguat in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction - The SOluble guanylate Cyclase stimulatoR in heArT failurE patientS With REDUCED EF (SOCRATES-REDUCED) Study
Mihai Gheorghiade1, Aldo P Maggioni2, Carolyn Lam3, Eliana Samano4, Elisabeth Kraigher-Krainer5, Gerasimos Filippatos6, Javed Butler7, Stephen J Greene8, Katharina Mueller9, Lothar Roessig9, Piotr Ponikowski10, Sanjiv Shah1, Scott D Solomon11, Burkert Pieske12; 1Dept of Medicine, Div of Cardiology, Northwestern Univ, Chicago, IL, 2ANMCO RESEARCH CENTER, ANMCO Rsch Cntr, Florence, Italy 3National Heart Cntr Singapore, National Heart Cntr Singapore, Singapore, Singapore 4Global Med Experts, Bayer S.A, Sao Paulo, Brazil 5Dept of Internal Medicine and Cardiology, Charité Univ Medicine Berlin , German Heart Cntr Berlin, Berlin, Germany 6Dept of Cardiology, Heart Failure, Athens Univ Hosp, Athens, Greece 7Cardiology, Stony Brook Univ, Stony Brook, NY, 8Dept of Medicine, Div of Cardiology, Duke Univ Med Cntr, Durham, NC, 9Global Development, Bayer Pharma AG, Wuppertal, Germany 10Dept of Cardiac Diseases, Med Univ, Wroclaw, Poland 11Cardiovascular Div, Brigham and Women's Hosp, Boston, MA, 12Dept of Internal Medicine and Cardiology, Charité Univ Medicine Berlin, Berlin, Germany
Introduction: Worsening chronic heart failure (WCHF) is a major public health problem. The objective of this study was to determine the safety, efficacy, and optimal dose of vericiguat, a soluble guanylate cyclase stimulator, in patients with WCHF with reduced left ventricular ejection fraction (LVEF). Methods: The SOCRATES-REDUCED trial was a phase II, dose-finding study of stable patients with LVEF<45% within 4 weeks of a WCHF event. Patients were randomized to placebo or 1 of 4 target doses of vericiguat (1.25 mg, 2.5 mg, 5 mg, 10 mg) for 12 weeks. The primary end point was the change from baseline to week 12 in log-transformed NT-proBNP level. Primary analysis specified pooled comparison of the 3 highest dose vericiguat arms with placebo. Pre-specified secondary analyses included effects of individual vericiguat dose arms and testing for a vericiguat dose-response relationship. Results: Overall, 456 patients were randomized and 351 patients were eligible for primary end point analysis. In primary analysis, change in log-transformed NT-proBNP from baseline to week 12 was not significantly different between the pooled vericiguat group and placebo (ratio of geometric means 0.885, p=0.151). In secondary analysis, there was a dose-response relationship (p=0.017) and the 10 mg vericiguat arm showed greater reductions in log-transformed NT-proBNP than placebo at 12 weeks (ratio of geometric means 0.779, p=0.048). In the 10 mg vericiguat arm, LVEF increased at 12 weeks compared to placebo (+3.7% vs +1.5%, p=0.021). There were no significant differences in blood pressure and heart rate at 12 weeks between 10 mg vericiguat and placebo arms and adverse events were not increased. At 12 weeks, numerically fewer patients in the 5 mg (11 patients) and 10 mg vericiguat groups (10 patients) experienced cardiovascular death or HF hospitalization compared to placebo (18 patients). Conclusions: Although the primary analysis of the primary end point was not achieved, compared to placebo, patients receiving vericiguat 10mg daily experienced a greater reduction in NT-proBNP, greater improvement in LVEF, and fewer clinical events. As titrated in this study, vericiguat doses up to 10 mg daily were safe and did not meaningfully influence blood pressure and heart rate at 12 weeks.
Author Disclosures: M. Gheorghiade: Consultant/Advisory Board; Modest; Abbott Laboratories, Astellas, AstraZeneca, Bayer HealthCare AG, CorThera, Cytokinetics, DebioPharm SA, Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Johnson & Johnson, Medtronic, Merck, Novartis Pharma AG, Otsuka Pharmaceuticals, Palatin Technologies, Pericor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Takeda, Trevena Therapeutics. A.P. Maggioni: Research Grant; Modest; Cardiorentis, Bayer, Novartis, Servier. C. Lam: Research Grant; Modest; Medtronic, Vifor Pharma. Research Grant; Significant; Boston Scientific. Consultant/Advisory Board; Modest; Bayer, Novartis, Takeda, Merck, Astra Zeneca, Janssen Research&Development, LL. E. Samano: Employment; Modest; Bayer SA. E. Kraigher-Krainer: Consultant/Advisory Board; Modest; Bayer Healthcare. G. Filippatos: Research Grant; Modest; European Union. Consultant/Advisory Board; Modest; Bayer, Novartis, Cardiorentis. J. Butler: Research Grant; Modest; National Institutes of Health, European Union. Consultant/Advisory Board; Modest; Amgen, Bayer, Cardiocell, Novartis, Boehringer-Ingelheim, Trevena, Relypsa, Z Pharma, Pharmain, Zensun. S.J. Greene: None. K. Mueller: Employment; Modest; Bayer Pharma AG. L. Roessig: Employment; Significant; Bayer Pharma AG. P. Ponikowski: Consultant/Advisory Board; Modest; Bayer Pharma AG. S. Shah: Research Grant; Significant; NIH, Actelion. Consultant/Advisory Board; Modest; AstraZeneca, Bayer, Alnylam. Consultant/Advisory Board; Significant; Novartis. S.D. Solomon: Consultant/Advisory Board; Modest; Bayer. B. Pieske: Speakers Bureau; Modest; Bayer Healthcare, Novartis, Stealth Peptides, AstraZeneca. Consultant/Advisory Board; Modest; Stealth Peptides, Daiichi Sankyo, BMS. Consultant/Advisory Board; Significant; Bayer Healthcare, Novartis.
Key Words: Clinical trials, Heart failure
20282 Remote Patient Management After Discharge of Hospitalized Heart Failure Patients: The Better Effectiveness After Transition - Heart Failure Study
Michael K Ong1, Patrick S Romano2, Sarah Edgington1, Andrew D Auerbach3, Harriet U Aronow4, Jeanne T Black5, Teresa De Marco3, Jose J Escarce1, Lorraine Evangelista6, Theodore G Ganiats7, Barry Greenberg8, Sheldon Greenfield9, Sherrie H Kaplan9, Asher Kimchi10, Honghu Liu11, Dawn Lombardo12, Carol M Mangione1, Majid Sarrafzadeh13, Kathleen Tong14, Gregg C Fonarow1, BEAT-HF Rsch Group; 1Medicine, UCLA, Los Angeles, CA, 2Medicine and Pediatrics, UC Davis, Sacramento, CA, 3Medicine, UCSF, San Francisco, CA, 4Nursing, Cedars-Sinai Med Cntr, Los Angeles, CA, 5Resource and Outcomes Management, Cedars-Sinai Med Cntr, Los Angeles, CA, 6Nursing, UC Irvine, Orange, CA, 7Family Medicine and Community Health, Univ of Miami, Miami, FL, 8Medicine, UCSD, San Diego, CA, 9Medicine, UC Irvine, Irvine, CA, 10Medicine, Cedars-Sinai Med Cntr, Los Angeles, CA, 11Dentistry, UCLA, Los Angeles, CA, 12Medicine, UC Irvine, Orange, CA, 13Computer Science, UCLA, Los Angeles, CA, 14Medicine, UC Davis, Sacramento, CA,
Introduction: Heart failure is a prevalent health problem associated with costly hospital readmissions. Transitional care programs have been shown to reduce readmissions but are costly to implement. Evidence regarding the effectiveness of telemonitoring in managing the care of this chronic condition is mixed. The Better Effectiveness After Transition - Heart Failure (BEAT-HF) study is a comparative effectiveness study designed to evaluate an intervention that combines a telephonic adaptation of care transition programs with telemonitoring. Hypothesis: a care transition intervention that includes pre-discharge education about heart failure and post-discharge telephone nurse coaching combined with home telemonitoring of weight, blood pressure, heart rate, and symptoms will reduce all-cause 180-day hospital readmissions for older adults hospitalized with heart failure. Methods: 1437 individuals admitted between October 2011 and September 2013 were enrolled in a multi-center, randomized controlled trial conducted at six academic health systems in California. Patients in the intervention group received intensive patient education using the 'teach-back' method and received instruction in using telemonitoring equipment. Following hospital discharge, they received up to nine scheduled health coaching telephone calls over 6 months from nurses located in a centralized call center. The nurses also called patients and patients' physicians in response to alerts generated by the telemonitoring system, based on predetermined parameters. Results: This presentation will report on the study primary outcome, readmission for any cause within 180 days, and on secondary outcomes including 30-day readmission, 30-day mortality, and 180-day mortality. Conclusions: BEAT-HF is one of the largest randomized controlled trials of telemonitoring in patients with heart failure, and the first explicitly to adapt the care transition approach and combine it with remote telemonitoring. The study population also includes patients with a wide range of demographic and socioeconomic characteristics.
Author Disclosures: M.K. Ong: None. P.S. Romano: None. S. Edgington: None. A.D. Auerbach: None. H.U. Aronow: None. J.T. Black: None. T. De Marco: None. J.J. Escarce: None. L. Evangelista: None. T.G. Ganiats: None. B. Greenberg: None. S. Greenfield: None. S.H. Kaplan: None. A. Kimchi: None. H. Liu: None. D. Lombardo: None. C.M. Mangione: None. M. Sarrafzadeh: None. K. Tong: None. G.C. Fonarow: Consultant/Advisory Board; Modest; Medtronic, Amgen, Janssen, Bayer, Boston Scientific. Other; Modest; Abbott. Research Grant; Significant; NIH, PCORI, AHRQ. Consultant/Advisory Board; Significant; Novartis.
Key Words: Heart failure, Transitions of care, Telemedicine
24294 Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure (COSMIC-HF): Final Results from a Double-blind, Randomized, Placebo-controlled, Multicenter Study
John R Teerlink1, G Michael Felker2, John JV McMurray3, Scott D Solomon4, Maria Laura Monsalvo5, Jason Legg5, Fady I Malik6, Narimon Honarpour5, for the COSMIC-HF Investigators; 1San Francisco Veterans Affairs Medical Center and School of Medicine University of California, San Francisco, San Francisco, CA, 2Duke University School of Medicine, Durham, NC, 3University of Glasgow, Glasgow, United Kingdom, 4Brigham & Women’s Hospital and Harvard Medical School, Boston, MA, 5Amgen Inc., Thousand Oaks, CA, 6Cytokinetics, Inc., South San Francisco, CA.
Background: Improving myocardial contractile function remains an attractive therapeutic target in patients with heart failure and reduced ejection fraction (HFrEF). Omecamtiv mecarbil (OM) is a novel selective cardiac myosin activator which when administered intravenously increases stroke volume by prolonging LV systolic ejection time (SET) without increasing heart rate or decreasing blood pressure. COSMIC-HF (NCT 01786512) was a Phase 2 study designed to select an oral modified-release formulation and dose of OM in patients with chronic HFrEF, and to characterize its pharmacokinetics (PK) and effects on cardiac function, as well as its safety and tolerability during 20 weeks of treatment. Methods: COSMIC-HF was a two-phase, multicenter, randomized, double-blind, placebo-controlled trial in outpatients with a history of optimally-treated chronic HF, LVEF ≤40%, and NT-proBNP ≥200 pg/mL (≥1200 pg/mL in patients with atrial fibrillation). Two cohorts were studied during the initial dose escalation phase; Cohort 1 was randomized 1:1:1:1 to 25 mg BID of one of three OM oral formulations or placebo for 7 days. Cohort 2 was randomized in the same manner to 50 mg BID. Based on PK, safety and tolerability, one formulation was advanced into the expansion phase, where patients were randomized 1:1:1 to receive the selected OM formulation in one of two treatment groups (25 mg BID or PK-based dose escalation to 50 mg BID) or placebo for 20 weeks. PK, echocardiographic and other clinical variables were assessed. Results: An oral formulation of OM was selected based on data from Cohorts 1 (n=49) and 2 (n=47) of the dose escalation phase (mean age 65 years, 21% female). The expansion phase completed enrollment and follow-up of 448 patients (mean age 63 years, 17% female). For the first time, the main results of COSMIC-HF, including Cmax/Ctrough (ng/ml), SET (msec), LV end-systolic dimension (mm), and adverse events will be presented. Conclusion: In addition to providing information on the PK of the selected oral formulation, COSMIC-HF will furnish some data addressing the hypothesis that oral administration of OM can increase SET and provide a sustained effect on cardiac performance in patients with chronic HFrEF.
Author Disclosures: J.R. Teerlink: Research Grant; Modest; Cytokinetics, Bayer, Trevena. Research Grant; Significant; Amgen and Novartis. Consultant/Advisory Board; Modest; Cytokinetics, Bayer, Trevena. Consultant/Advisory Board; Significant; Amgen and Novartis. G. Felker: Research Grant; Significant; Amgen, Roche Diagnostics, Novartis, Otuska and NHLBI. Consultant/Advisory Board; Significant; served as a consultant for Amgen, Novartis, Roche Diagnostics, Singulex, Trevena, Celladon, Bristol Meyers Squibb, Merck and Medtronic. J.J. McMurray: Employment; Significant; Glasgow University has been paid by Cytokinetics/Amgen for his time spent working on the clinical trial program with omecamtiv mecarbil. Other; Modest; Travel accommodations costs paid by Cytokinetics/Amgen in relation to advisory board and clinical trial meetings about omecamtiv mecarbil. S.D. Solomon: Other Research Support; Modest; Amgen. Consultant/Advisory Board; Modest; Amgen. M.L. Monsalvo: Employment; Significant; employee and stockholder of Amgen. J. Legg: Employment; Significant; employee and stockholder of Amgen. F.I. Malik: Employment; Significant; Stockholder of Cytokinetics. N. Honarpour: Employment; Significant; employee and stockholder of Amgen.
Prevention and Rehabilitation
Decreasing the Global Burden of Disease: Breakthroughs in Prevention
15602 The Efficacy and Safety of Varenicline, a Selective Alpha4beta2 Nicotinic Receptor Partial Agonist, for Smoking Cessation in Patients Hospitalized With Acute Coronary Syndrome: A Randomized Controlled Trial
Mark J Eisenberg1, Sarah B Windle2, Nathalie Roy3, Wayne Old4, François Grondin5, Iqbal Bata6, Ayman Iskander7, Claude Lauzon8, Nalin Srivastava9, Adam Clarke10, Daniel Cassavar11, Danielle Dion12, Herbert Haught13, Shamir Mehta14, Jean-François Baril15, Charles Lambert16, Mina Madan17, Beth L Abramson18, Payam Dehghani19; 1Cardiology and Clinical Epidemiology, Jewish General Hosp / McGill Univ, Montreal, Canada 2Cntr for Clinical Epidemiology, Jewish General Hosp, Montreal, Canada 3Cardiology, CSSS Chicoutimi, Chicoutimi, Canada 4Cardiology, Sentara Cardiovascular Rsch Institute, Norfolk, VA, 5Cardiology, Clinique de Cardiologie de Lévis, Lévis, Canada 6Cardiology, Queen Elizabeth II Health Sciences Cntr, Halifax, Canada 7Cardiology, SJH Cardiology Associates and St. Joseph's Hosp, Liverpool, NY, 8Cardiology, CISSS - Chaudière-Appalaches, Thetford Mines, Canada 9Cardiology, Spartanburg Regional Med Cntr, Spartanburg, SC, 10Cardiology, Valley Regional Hosp, Kentville, Canada 11Cardiology, ProMedica Toledo Hosp, Toledo, OH, 12Cardiology, CISSS de Chaudière Appalaches - site Hôpital St-Georges, Saint-Georges, Canada 13Cardiology, Heart Cntr Rsch, Huntsville, AL, 14Cardiology, Hamilton Health Sciences, Hamilton, Canada, 15Cardiology, Dr. Georges-L.-Dumont Univ Hosp Cntr, Moncton, Canada, 16Cardiology, Florida Hosp Pepin Heart Institute, Tampa, FL, 17Cardiology, Sunnybrook Health Sciences Cntr, Toronto, Canada, 18Cardiology, St. Michaels Hosp / Univ of Toronto, Toronto, Canada, 19Cardiology, Prairie Vascular Rsch Network / Univ of Saskatchewan, Regina, Canada
Background: Less than a third of smokers hospitalized with an acute coronary syndrome (ACS) remain abstinent following discharge. We assessed whether varenicline, begun in-hospital, is efficacious for smoking cessation following ACS. Methods: We conducted a multi-center, double-blind, randomized, placebo-controlled trial in which smokers hospitalized with an ACS were randomized to varenicline (1.0 mg twice daily) or matched placebo for 12 weeks. All patients received low-intensity counseling. The primary endpoint was point prevalence smoking abstinence assessed at 24 weeks by 7-day recall and biochemical validation using expired carbon monoxide. Results: A total of 302 patients were randomized in the US and Canada. Demographic, smoking, and clinical characteristics were well balanced between the two study arms. Patients were primarily male (75.2%) with a mean age of 55.0 ± 9.3 years. On average, patients had smoked 35.9 ± 11.6 years and were smoking a mean of 21.4 ± 10.6 cigarettes/day at the time of ACS. Scores on the Fagerström Test of Nicotine Dependence ranged from 0 to 10, with 80.4% of patients having scores ≥ 4 indicating moderate or severe dependence on nicotine. Patients presented with ST-segment elevation myocardial infarction (56.0%), non-ST segment elevation myocardial infarction (37.8%), and unstable angina (6.3%). At 24 weeks, patients randomized to varenicline had significantly higher rates of smoking abstinence and reduction than patients randomized to placebo. For the primary endpoint of point prevalence smoking cessation, 47.3% of varenicline patients were abstinent versus 32.5% of placebo patients (number needed to treat = 6.8). Continuous abstinence rates were 35.8% and 25.8%, respectively (number needed to treat = 10.0). Reduction ≥50% in number of cigarettes smoked/day were 67.4% and 55.6%, respectively (number needed to treat = 8.5). Adverse event rates within 30 days of study drug discontinuation were similar between groups (serious adverse events: varenicline 11.3%, placebo 11.3%; major adverse cardiovascular events: varenicline 4.0%, placebo 4.6%). Conclusions: Varenicline, initiated in-hospital following ACS, is efficacious for smoking cessation.
Author Disclosures: M.J. Eisenberg: None. S.B. Windle: None. N. Roy: None. W. Old: None. F. Grondin: None. I. Bata: None. A. Iskander: None. C. Lauzon: None. N. Srivastava: None. A. Clarke: None. D. Cassavar: None. D. Dion: None. H. Haught: None. S. Mehta: None. J. Baril: None. C. Lambert: None. M. Madan: None. B.L. Abramson: None. P. Dehghani: None.
Key Words: Smoking, Acute coronary syndromes, Clinical trials
20189 Impact of a Comprehensive Lifestyle Peer-group-based Intervention on Cardiovascular Risk Factors: A Randomized Controlled Trial
Emilia G. Pardo1, Juan Miguel Fernandez Alvira2, Marta Vilanova3, Domingo Haro4, Ramona Martínez5, Isabel Carvajal6, Vanesa Carral4, Carla Rodríguez7, Mercedes de Miguel1, Patricia Bodega1, Gloria Santos-Beneit1, José L Peñalvo8, Iñaki Marina9, Napoleón Pérez10, Marian DalRe11, Carmen Villar12, Teresa Robledo12, Rajesh Vedanthan13, Sameer Bansilal13, Valentin Fuster13; 1Scientific Dept, SHE Foundation, Madrid, Spain 2Dept of epidemiology, atherothrombosis and imaging, National Cntr for Cardiovascular Rsch (CNIC), Madrid, Spain 3Scientific Dept, SHE Foundation, Barcelona, Spain 4Dept of Pedagogy, SHE Foundation, Barcelona, Spain 5Coordination, SHE Foundation, Barcelona, Spain 6Director, SHE Foundation, Madrid, Spain 7Dept of Pedagogy, SHE Foundation, Madrid, Spain 8Friedman Sch of Nutrition Science and Policy, Tufts Univ, Boston, MA, 9Internal Medicine, Catalan Health Institute, Barcelona, Spain 10NAOS Strategy, Spanish Agency for Consumer Affairs, Food safety and Nutrition (AECOSAN), Madrid, Spain 11NAOS Strategy, Spanish Agency for Consumers Affairs, Food Safety and Nutrition (AECOSAN), Spain, Spain 12NAOS Strategy, Spanish Agency for Consumers Affairs, Food Safety and Nutrition (AECOSAN), Madrid, Spain 13Dept of Medicine, Icahn Sch of Medicine at Mount Sinai, New York, NY,
Introduction: Cardiovascular diseases stem from modifiable risk factors. Peer support is a proven strategy for many chronic illnesses. Randomized trials assessing the efficacy of this strategy for global CV risk factor modification are lacking. Hypothesis: We assessed the hypothesis that a peer-group strategy helps improve healthy behaviors in individuals with CV risk factors. Methods: We recruited 543 adults aged 25-50 years with at least one risk factor: hypertension (20%), overweight (82%), smoking (31%) or physical inactivity (81%). Subjects were randomized 1:1 to a peer-group based intervention group (IG) or a self-management control group (CG) for 12 month. Peer-elected leaders moderated monthly meetings involving role-play, brainstorming and activities to address emotions, diet and exercise. The primary outcome was mean change in a composite score related to Blood pressure, Exercise, Weight, Alimentation and Tobacco (Fuster-BEWAT score, 0-15). Multilevel models with municipality as cluster variable were applied to assess differences between groups. Results: Participants’ mean age was 42 ± 6 years, 71% female, with mean baseline score of 8.42 ± 2.35. After 1 year, the mean BEWAT score values were significantly higher in the IG (n=277) than CG (n=266) [IG mean=8.84 (8.37-9.32); CG mean=8.17 (7.55-8.79), p=0.02]. The increase in the overall score was significantly larger in the IG compared to the CG [diff: 0.75(0.32-1.18); p: 0.02]. The mean improvement in the individual components was uniformly greater in the IG, with a significant difference for the tobacco component (Table). Conclusion: The peer-group intervention had beneficial effects on CV risk factors, with significant improvements in the overall score and specifically on tobacco cessation. A follow-up assessment will be performed 1-year after the final assessment reported here in order to to determine long-term sustainability of the improvements associated with peer-group intervention.
Author Disclosures: E. G. Pardo: None. J. Fernandez Alvira: None. M. Vilanova: None. D. Haro: None. R. Martínez: None. I. Carvajal: None. V. Carral: None. C. Rodríguez: None. M. de Miguel: None. P. Bodega: None. G. Santos-Beneit: None. J.L. Peñalvo: None. I. Marina: None. N. Pérez: None. M. DalRe: None. C. Villar: None. T. Robledo: None. R. Vedanthan: None. S. Bansilal: None. V. Fuster: None.
20989 Clinical Trial of a Mobile Health Intervention for Simultaneous versus Sequential Diet and Activity Change
Bonnie Spring1, Christine A Pellegrini1, H. G McFadden1, Angela Pfammatter1, Juned Siddique1, Donald Hedeker2; 1Preventive Medicine, Northwestern Univ, Chicago, IL, 2Public Health Sciences, Univ of Chicago, Chicago, IL,
Background: Because unhealthy behaviors often co-occur, the Make Better Choices 1 trial tested whether increasing healthy or decreasing unhealthy diet and activity behaviors maximized overall healthy lifestyle change in adults with all of 4 risk behaviors: low fruits/vegetables, high saturated fat, low moderate-vigorous physical activity, high leisure screen time. Coaching to increase fruits/vegetables and decrease sedentary leisure also spontaneously reduced saturated fat intake, but did not increase physical activity. Hypotheses: Make Better Choices 2 tested the hypothesis that adding physical activity coaching sequentially rather than simultaneously would maximize healthy change. Methods: Adults (n=212) with all 4 risk behaviors were randomized to 3 different interventions that used a smartphone app, wireless accelerometer, and remote coaching to: increase physical activity while changing fruits/vegetables and sedentary leisure (Simultaneous), improve fruits/vegetables and sedentary leisure first, followed by physical activity (Sequential), or improve stress and sleep (Control). Intent to treat analyses using linear mixed-effects models examined change in the behaviors from baseline through 6 and 9 month follow-up. Results: Attrition through 9 month follow-up was 16% and not differential across treatments. At 9 month follow-up, there were significant differences between the control group and both the simultaneous and sequential treatment groups in terms of daily increased fruit/vegetable intake (mean difference=5.9 credits, 95% CI [4.5, 7.2]), decreased leisure screen time (mean difference=126.9 min, 95% CI [100.3, 153.4]), and decreased saturated fat intake (mean difference=3.7%, 95% CI [2.1, 5.4]). At 6 month follow-up there was increased daily moderate-vigorous physical activity in the treatment groups (mean difference=15.8 min, 95% CI [0.7, 30.9]). Conclusions: A mobile health intervention incorporating smartphone technology and remote coaching can produce sustained improvements in multiple diet and activity lifestyle behaviors regardless of whether moderate vigorous physical activity is targeted simultaneously or sequentially with other diet and activity behaviors.
Author Disclosures: B. Spring: None. C.A. Pellegrini: None. H.G. McFadden: None. A. Pfammatter: None. J. Siddique: None. D. Hedeker: None.
20980 The Effect of Disclosing Genomic Risk of Coronary Heart Disease on Low-density Lipoprotein Cholesterol Levels: The Myocardial Infarction Genes (MI-GENES) Study
Iftikhar J Kullo1, Hayan Jouni1, Iyad Isseh1, Erin Austin1, Teresa Kruisselbrink2, Sherry-Ann Brown3, Robert C Green4, Victor Montori5, Raad Haddad1, Daniel Schaid6, Ulrich Broeckel7, Kent R Bailey8; 1Div of Cardiovascular Diseases, Dept of Medicine, Mayo Clinic, Rochester, MN, 2Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN, 3Internal Medicine, Mayo Clinic, Rochester, MN, 4Brigham and Women's Hosp and Harvard Med Sch, Mayo Clinic, Boston, MA, 5Div of Endocrinology, Dept of Medicine, Mayo Clinic, Rochester, MN, 6Div of Biomedical Statistics and Informatics, Dept of Health Science Rsch, Mayo Clinic, Rochester, MN, 7Human and Molecular genetics Cntr, Med College of Wisconsin, Milwaukee, WI, 8Dept of Health Sciences Rsch, Mayo Clinic, Rochester, MN,
Background: Whether knowledge of genetic risk for coronary heart disease (CHD) affects health-related outcomes is unknown. We investigated whether disclosure of a genetic risk score for CHD lowers low-density lipoprotein cholesterol (LDL-C) levels. Methods: The randomized clinical trial was conducted in 203 residents of Olmsted County, who were 45-65 years old, at intermediate risk for CHD, and not on statins. Participants were randomized to receive their 10-year probability of CHD based either on conventional risk factors (CRS) or CRS plus a genetic risk score (+GRS). Participants in the +GRS group were stratified as having high (+H-GRS) or average/low (+L-GRS) genetic risk score. We compared the primary endpoint of LDL-C levels at 6 months following disclosure of CHD risk in the study arms. Secondary outcomes included dietary fat intake, physical activity, anxiety levels and statin use. Results: Participants [n= 203, mean age 59.4 (5) years, 49% men, mean 10-year CHD risk 8.5 (4.1)%] were allocated to receive either CRS (n=100) or +GRS (n=103). At the end of the study, the +GRS group had lower LDL-C levels than the CRS group [96.5 (32.7) vs. 105.9 (33.3) mg/dL; P=0.04]. +H-GRS participants had lower LDL-C levels [92.3 (32.7) mg/dL] than CRS participants (P=0.02) but not +L-GRS participants [100.9 (32.2) mg/dL; P=0.18]. The overall downward longitudinal trend in LDL-C was significantly greater in +GRS than in CRS (P=0.04). Use of statins was greater in the +GRS group than in the CRS group (39% vs. 22%, P<0.01). No significant differences in dietary fat intake, physical activity and anxiety levels were present. Conclusion: Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone.
Author Disclosures: I.J. Kullo: None. H. Jouni: None. I. Isseh: None. E. Austin: None. T. Kruisselbrink: None. S. Brown: None. R.C. Green: None. V. Montori: None. R. Haddad: None. D. Schaid: None. U. Broeckel: None. K.R. Bailey: None.
20238 Empagliflozin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk
Silvio E Inzucchi1, Christoph Wanner2, John M Lachin3, David Fitchett4, Erich Bluhmki5, Stefan Hantel5, Michaela Mattheus6, Theresa Devins7, Odd Erik Johansen8, Hans Juergen Woerle9, Uli C Broedl9, Bernard Zinman10; 1Section of Endocrinology, Yale Univ Sch of Medicine, New Haven, CT, 2Dept of Medicine, Div of Nephrology, Würzburg Univ Clinic, Würzburg, Germany 3The Biostatistics Cntr, The George Washington Univ, Rockville, MD, 4Div of Cardiology, St Michael's Hosp, Toronto, Canada 5Global biometrics and datamanagement, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany 6Global biometrics and datamanagement, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany 7Clinical operations, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, 8Therapeutic Area Metabolism, Boehringer Ingelheim Norway KS, Asker, Norway 9Therapeutic Area Metabolism, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany 10Lunenfeld-Tanenbaum Rsch Institute and Div of Endocrinology, Mount Sinai Hosp and Univ of Toronto, Toronto, Canada
Patients with type 2 diabetes mellitus (T2DM) and established cardiovascular (CV) complications are at particularly high risk of further CV events, including hospitalization for heart failure (HF) and premature death. However, the long-term benefit of glucose-lowering therapies on CV outcomes has been highly controversial. We recently reported the initial results of EMPA-REG OUTCOME™ (NCT01131676.) In this trial, a total of 7028 patients with overt CV disease from 42 countries and 590 sites were randomized between September 2010 and April 2013 to one of two doses of the SGLT2 inhibitor empagliflozin (empa; 10 or 25 mg) or placebo. 7020 patients were treated and included in the primary analysis. At baseline, the mean HbA1c was 8.1%, BMI 30.6 kg/m2, and 71.5% were males. Virtually all (99.2%) patients had a prior history of CVD: MI 46.6%, CABG 24.8%, stroke 23.3%, and peripheral arterial disease 20.8%. There was high usage of evidence-based CV therapies, such as statins, renin-angiotensin system (RAS) blockers, and aspirin. All CV events were adjudicated by an independent, blinded expert committee. Nearly 97% of the original cohort completed the study, and vital status was known in >99%. Empa (pooled doses) demonstrated superiority to placebo for the primary outcome, 3-point MACE, composed of time to first event of the composite of non-fatal MI, non-fatal stroke or CV death (HR 0.86 [95% CI, 0.74, 0.99; p=0.0382.]) This was driven primarily by a 38% relative risk reduction (RRR) in CV death (p<0.0001.) Empa also reduced the secondary endpoints of HF hospitalization (HFH) (RRR 35%, p=0.0017) and all-cause death (RRR 32%, p<0.0001). The presentation will include the additional outcomes of HF mortality, HFH or CV death, and recurrent HFH in the entire cohort. In addition we will describe the baseline characteristics and subsequent outcomes in patients with versus without a history of HF prior to trial enrollment. These expanded results from the first-in-class, large CV outcome trial involving an SGLT2 inhibitor will further inform clinicians of empagliflozin’s CV effectiveness, including mortality reduction, in high-risk patients with T2DM.
Author Disclosures: S.E. Inzucchi: Research Grant; Significant; Takeda. Consultant/Advisory Board; Modest; Novo Nordisk, Eisai, Lexicon, Intarcia, Astra Zeneca, Janssen, Merck, Sanofi/Regeneron, Transtech Pharma. Consultant/Advisory Board; Significant; Boehringer Ingelheim. C. Wanner: Research Grant; Significant; Genzyme. Honoraria; Modest; Boehringer Ingelheim, Merck Sharp & Dome, Sanofi, Amgen, Genzyme. Consultant/Advisory Board; Modest; Boehringer Ingelheim, Sanofi, Amgen. J.M. Lachin: Consultant/Advisory Board; Modest; Boehringer Ingelheim, Astra Zeneca, Janssen, Merck. D. Fitchett: Speakers Bureau; Modest; Merck, Astra Zeneca. Honoraria; Modest; Merck, Astra Zeneca, Sanofi. Consultant/Advisory Board; Modest; Boehringer Ingelheim, Sanofi, Amgen, Merck, Astra Zeneca. Other; Modest; Novo Nordisk. E. Bluhmki: Employment; Significant; Boehringer Ingelheim. S. Hantel: Employment; Significant; Boehringer Ingelheim. M. Mattheus: Employment; Significant; Boehringer Ingelheim. T. Devins: Employment; Significant; Boehringer Ingelheim. O. Johansen: Employment; Significant; Boehringer Ingelheim. H. Woerle: Employment; Significant; Boehringer Ingelheim. U.C. Broedl: Employment; Significant; Boehringer Ingelheim. B. Zinman: Research Grant; Significant; Merck, Boehringer Ingelheim, Novo Nordisk. Consultant/Advisory Board; Modest; Eisai, Astra Zeneca, Janssen, Eli Lilly, Sanofi, Takeda, Amgen. Consultant/Advisory Board; Significant; Boehringer Ingelheim, Merck, Novo Nordisk.
Intervention and Surgery
ACS and PCI: The Continuum of Care
19896 Providing Rapid Out of Hospital Acute Cardiovascular Treatment (PROACT-4)
Justin A Ezekowitz1, Robert C Welsh1, Dale Weiss2, Michael Chan3, William Keeble4, Fadi Khadour5, Sanjay Sharma6, Wayne Tymchak7, Sunil Sookram8, Neil Brass9, Darren Knapp10, Thomas I Koshy11, Yinggan Zheng1, Paul W Armstrong1; 1Canadian VIGOUR Cntr, Univ of Alberta, Edmonton, Canada 2EMS Operations, Alberta Health Services, Edmonton, Canada 3CK Hui Heart Cntr, Royal Alexandra Hosp, Edmonton, Canada 4Cardiology, Misericordia Hosp, Edmonton, Canada 5Cardiology, Sturgeon Community Hosp, St. Albert, Canada 6Cardiology, Grey Nuns Community Hosp, Edmonton, Canada 7Mazankowski Alberta Heart Institute, Univ of Alberta, Edmonton, Canada 8Cardiology, Emergency and Critical Care, Univ of Alberta Hosp, Edmonton, Canada 9Cardiology, Royal Alexandra Hosp, Edmonton, Canada 10Vital Heart Response, Alberta Health Services, Edmonton, Canada 11Scientific Affairs, Alere, San Diego, CA,
Introduction: Early troponin testing has transformed the diagnosis of patients presenting to the emergency department (ED) with acute cardiovascular (CV) symptoms. Whether point-of-care (POC) troponin testing in the ambulance can further accelerate the time to diagnosis is unknown. We conducted a randomized trial of POC troponin testing in the ambulance. Methods: Patients with chest pain (CP) presenting via ambulance were included; STEMI patients or those with a clear non-CV cause for their symptoms were excluded. Patients were randomized to usual care or POC-Troponin. The POC-Troponin arm had a high-sensitivity troponin (99%ile: 0.02 ng/ml) drawn pre-hospital and analyzed on a POC device in the ambulance: results were available to the paramedic and ED staff. The final diagnosis was centrally adjudicated. The primary endpoint was time from first medical contact to final ED disposition i.e. discharge from ED or admission to hospital. Results: We randomized 601 patients in 19 months; 296 to usual care and 305 to POC-Troponin. Patients were 57% male, median age of 66 years (53-78), 30% had prior CAD and 25% had diabetes. After the 911 call, the first troponin was available a median of 139 min (101-218) in usual care and 38 min (28-55) in POC-Troponin. In POC-Troponin, the troponin was >0.01 ng/ml in 17.4% and >0.03 ng/ml in 9.8%. In the entire cohort and after diagnosis adjudication, patients had angina (n=24), acute coronary syndrome (n=112), acute heart failure (n=16), other cardiovascular (n=27), chest pain not yet diagnosed (n=289) and other (n=126) causes for chest pain. Patients spent a median of 8.97 hours (6.47-10.98) from first medical contact to final disposition, and 165 (27.4%) were admitted to hospital. The primary endpoint was shorter in patients randomized to POC-Troponin (median 8.75 hours [6.2 - 10.77] compared to usual care (median 9.14 hours [6.69 - 11.17], p=0.05). There was no difference in the secondary endpoint of repeat ED visits, hospitalizations or death in the next 30 days. Conclusions: In this broad population of patients with CP, POC troponin in the ambulance accelerated the time to final disposition. The potential for enhanced and more cost effective early ED triage of the majority of low-risk patients with CP is an unrealized opportunity.
Author Disclosures: J.A. Ezekowitz: None. R.C. Welsh: None. D. Weiss: None. M. Chan: None. W. Keeble: None. F. Khadour: None. S. Sharma: None. W. Tymchak: None. S. Sookram: None. N. Brass: None. D. Knapp: None. T.I. Koshy: Employment; Significant; Alere Inc.. Y. Zheng: None. P.W. Armstrong: None.
Key Words: Clinical trials, Troponin, Chest pain centers, Emergency medical services (EMS)
12184 Clinical Outcomes of Intravascular Ultrasound Guided Everolimus-Eluting Stents Implantation in Long Coronary Lesions
Myeong-Ki Hong1, Sung-Jin Hong2, Byeong-Keuk Kim2, Dong-Ho Shin2, Jung-Sun Kim2, Young-Guk Ko2, Donghoon Choi2, Yangsoo Jang2; 1Div of Cardiology, Severance Cardiovascular Hosp and Cardiovascular Rsch Institute, Yonsei Univ College of Medicine, Seoul, Korea, Republic of 2Div of Cardiology, Severance Cardiovascular Hosp, Yonsei Univ College of Medicine, Seoul, Korea, Republic of
Use of intravascular ultrasound (IVUS) promotes better clinical outcomes for coronary intervention in complex coronary lesions. However, randomized data demonstrating the clinical usefulness of IVUS is limited in lesions treated with second-generation drug-eluting stents. The objective of this trial is to determine whether the long-term clinical outcomes of IVUS-guided drug-eluting stent implantation are superior to that of angiography-guided implantation in patients with long coronary lesions. A prospective, randomized, multicenter trial was conducted at 20 centers in 1,400 patients with long coronary lesions (implanted stent ≥28 mm in length) between October 2010 and July 2014. Patients were randomly assigned to receive IVUS- (n=700) or angiography-guided (n=700) everolimus-eluting stent implantation. Primary outcome measure is the composite of major adverse cardiac events, including cardiac death, target lesion-related myocardial infarction, or ischemia-driven target lesion revascularization at 1 year. Major adverse cardiac events at 1 year occurred in 19 patients (2.9%) receiving IVUS-guidance and in 39 patients (5.8%) receiving angiography-guidance (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.28-0.83; p=0.009) (Figure). The difference was mainly driven by a lower risk of target lesion revascularization (17 [2.5%] vs 33 [5.0%], respectively; HR, 0.51; 95% CI, 0.28-0.91; p=0.022) in patients receiving IVUS-guidance compared with angiography-guidance. Cardiac death and target lesion-related myocardial infarction were not significantly different between the two groups. In conclusion, among patients requiring long coronary stent implantation, the use of IVUS-guided everolimus-eluting stent implantation resulted in a significantly lower rate of the composite of major adverse cardiac events at 1 year compared with patients who received angiography-guided everolimus-eluting stent implantation.
Author Disclosures: M. Hong: None. S. Hong: None. B. Kim: None. D. Shin: None. J. Kim: None. Y. Ko: None. D. Choi: None. Y. Jang: None.
Key Words: Drug eluting stents, Intravascular ultrasound/Doppler, Coronary artery disease
19689 Long-Term Tolerability of Ticagrelor in the PEGASUS-TIMI 54 Trial
Marc P Bonaca1, Deepak L Bhatt1, Ton Oude Ophuis2, P. Gabriel Steg3, Robert Storey4, Marc Cohen5, Julia Kuder1, KyungAh Im1, Giulia Magnani1, Andrej Budaj6, Pierre Theroux7, Christian Hamm8, Jindřich Špinar9, Robert Kiss10, Anthony Dalby11, Diego Ardissino12, Frederic Kontny13, Philip Aylward14, Eva C Jensen15, Peter Held15, Marc S Sabatine1; 1MEDICINE, CARDIOVASCULAR MEDICINE, TIMI Study Group, Brigham and Womens Hosp, Boston, MA, 2CWZ Hosp, CWZ Hosp, Nijmegen, Netherlands 3Département de Cardiologie, Hôpital Bichat, Assistance Publique - Hôpitaux de Paris, Paris, France 4Univ of Sheffield, Univ of Sheffield, Sheffield, United Kingdom 5Cardiovascular Div, Dept of Medicine, Beth Israel Med Cntr, Mount Sinai Sch of Medicine, New York, NY, 6Postgraduate Med Sch, Grochowski Hosp, Warsaw, Poland 7Montreal Heart Institute, Montreal Heart Institute, Montréal, Canada 8Cardiology, Kerckhoff Heart Cntr, Bad Nauheim, Germany 9Internal cardiology department, Univesity Hosp and Med Faculty, Brno, Czech Republic 10Cardiology, Military Hosp, Budapest, Hungary 11Cardiology, Milpark Hosp, Johannesburg, South Africa 12Cardiology, Azienda Hosp-Univ of Parma, Parma, Italy 13Dept. of Cardiology, Stavanger Univ Hosp, Stavanger, Norway 14Div of Medicine, Cardiac & Critical Care Services, Flinders Med Cntr, Bedford Park, Australia 15R&D, AstraZeneca, Mölndal, Sweden
Objective: Ticagrelor initiated in patients with prior MI reduced the incidence of CV death, MI, or stroke by 15-16% in PEGASUS-TIMI 54. Premature discontinuation was higher with ticagrelor than placebo. We investigated the rates and reasons for drug discontinuation and the long-term efficacy of ticagrelor in patients who stayed on therapy. Methods: Rates and causes of treatment discontinuation were evaluated overall and by timing relative to randomization. Efficacy analyses were performed examining events occurring while pts were on study drug and up to 7 days after the last dose. Results: Over the duration of the trial (median 33 mos), 32%, 29%, and 21% of patients stopped study drug in the ticagrelor 90 mg, 60 mg and placebo arms, respectively (P<0.001). 10-11% of patients in each arm stopped study drug because of patient decision or administrative reason. Conversely, rates of study drug discontinuation due to an adverse event (AE) were 8.9% in the placebo arm, but 19% and 16.4% in the ticagrelor 90 mg and 60 mg arms (P<0.01). The most frequent AEs leading to discontinuation were bleeding (6.5%, 5.1%, 1.2%, p<0.001) and dyspnea (6.2%, 4.3%, 0.7%, p<0.001). In the ticagrelor arms, only 14% of bleeds were major and only 12% of cases of dyspnea were severe. The rates of AEs leading to drug discontinuation and the differences between arms were greater in the first year and then greatly attenuated thereafter (Fig Left). Overall, in terms of events while on study drug, ticagrelor substantially reduced the risk of CV death, MI or stroke (HR 0.79, 95% CI 0.70-0.88, P<0.0001) as well as each of the individual components and was associated with lower all-cause mortality (Fig Right). Conclusion: When initiated in stable patients with prior MI, discontinuation of ticagrelor was driven primarily by non-severe AEs occurring early after randomization. In patients who remained on study drug, there was a substantial benefit to ticagrelor, suggesting counseling on adherence could improve outcomes.
Author Disclosures: M.P. Bonaca: Research Grant; Significant; Grant support to TIMI from AstraZeneca and Merck. Consultant/Advisory Board; Modest; AstraZeneca, MERCK, Bayer, Roche Diagnostics. D.L. Bhatt: Research Grant; Significant; AstraZeneca. T. Oude Ophuis: Speakers Bureau; Modest; AstraZeneca. Consultant/Advisory Board; Modest; AstraZeneca. P. Steg: Research Grant; Significant; Sanofi, Servier. Consultant/Advisory Board; Modest; Amarin (Personal Fees), Bayer (Personal Fees), Boehringer Ingelheim (Personal Fees), Bristol-Myers Squibb (Personal Fees), CSL-Behring (Personal Fees), Daiichi-Sankyo (Personal Fees), Lilly (Personal Fees), Merck Sharpe Dohme (Personal Fees), Janssen (Personal Fees), Novartis (Personal Fees), Medtronic (Personal Fees), Pfizer (Personal Fees), The Medicines Company (Personal Fees), GlaxoSmithKline (Personal Fees). Other; Significant; AstraZeneca, Sanofi, Servier. R. Storey: Research Grant; Significant; AstraZeneca, Merck. Consultant/Advisory Board; Modest; AstraZeneca (personal fees), Aspen (personal fees), PlaqueTec (personal fees), The Medicines Company (personal fees), ThermoFisher Scientific (personal fees), Merck (personal fees), Correvio (personal fees), Roche (personal fees), Regeneron (personal fees), Sanofi Aventis (personal fees), Accumetrics (personal fees), Daiichi Sankyo/Eli Lilly (personal fees). Other; Modest; a patent related to study results pending. M. Cohen: Research Grant; Modest; Maquet. Consultant/Advisory Board; Modest; Maquet. J. Kuder: None. K. Im: None. G. Magnani: None. A. Budaj: Research Grant; Significant; AstraZeneca, GlaxoSmithKline, Bristol Myers Squibb/Pfizer;, Sanofi-Aventis, Boehringer Ingelheim, Novartis, Eisai. Other; Modest; AstraZeneca (personal fees), Bristol Myers Squibb/Pfizer (personal fees), GlaxoSmithKline (personal fees). P. Theroux: Research Grant; Significant; AstraZeneca. C. Hamm: Speakers Bureau; Modest; AstraZeneca. Consultant/Advisory Board; Modest; AstraZeneca. J. Špinar: None. R. Kiss: None. A. Dalby: Speakers Bureau; Modest; AstraZeneca. Consultant/Advisory Board; Modest; AstraZeneca. D. Ardissino: None. F. Kontny: None. P. Aylward: None. E.C. Jensen: Employment; Significant; AstraZeneca. P. Held: Employment; Significant; AstraZeneca. M.S. Sabatine: Research Grant; Modest; Abbott Laboratories, Amgen, AstraZeneca, Critical Diagnostics, Daiichi-Sankyo, Eisai, Gilead, GlaxoSmithKline, Intarcia, Merck, Roche Diagnostics, Sanofi-aventis, Takeda. Consultant/Advisory Board; Modest; Alnylam, Amgen, AstraZeneca, Cubist, CVS Caremark, Intarcia, Merck. Research Grant; Significant; Consultant/Advisory Board; Significant; Modest.
Key Words: Ticagrelor, Coronary heart disease, Antiplatelet drugs, Prevention, Myocardial infarction
20297 Individualizing Treatment Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: An Analysis of the DAPT Study
Robert W Yeh1, Eric Secemsky1, Dean J Kereiakes2, Anthony Gershlick3, David J Cohen4, John A Spertus5, Philippe G Steg6, Donald E Cutlip7, Patricia K Apruzzese8, Joseph M Massaro9, Laura Mauri10; 1Cardiology, Massachusetts General Hosp, Boston, MA, 2The Lindner Rsch Cntr, The Christ Hosp Heart and Vascular Cntr, Cincinnati, OH, 3Cardiovascular Sciences, Univ of Leicester, Leicester, United Kingdom 4Cardiology, Saint Luke’s Mid America Heart Institute, Kansas City, MO, 5Cardiovascular Rsch, Saint Luke’s Mid America Heart Institute, Kansas City, MO, 6Medicine, Université Paris-Diderot, Paris, France 7Clinical Investigations, Harvard Clinical Rsch Institute, Boston, MA, 8Biostatistics, Harvard Clinical Rsch Institute, Boston, MA, 9Biostatistics, Boston Univ Sch of Public Health, Boston, MA, 10Medicine, The Brigham and Women's Hosp, Boston, MA,
Background: Extended duration dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) reduces stent thrombosis (ST) and myocardial infarction (MI) but increases bleeding. Strategies to individualize DAPT treatment duration are therefore needed to optimize patient outcomes. Methods: The DAPT Study randomized 11,648 PCI patients who completed 12 months of DAPT to continued thienopyridine plus aspirin vs aspirin alone. Multivariable models to predict the composite of ST or MI (ischemia model) and GUSTO moderate/severe bleeding (bleeding model) were constructed using Cox regression. The predicted absolute reduction in ischemia and increase in bleeding assuming treatment with continued thienopyridine vs placebo was estimated for each patient, and the difference between these values was calculated (“benefit-risk difference”). The correlation between patient predicted ischemic and bleeding events was evaluated using Spearman’s Rho. Results: Models to predict MI or ST and bleeding events beyond 12 months had moderate discrimination (c-stat 0.70 and 0.68, respectively). The predicted risks of ischemic and bleeding events between 12 and 30 months were weakly correlated (rho = 0.18). The benefit-risk difference for continued thienopyridine varied from -3.7% to 19.3%, based on patient age, presentation with MI, prior PCI, heart failure/ejection fraction, diabetes, smoking status, stent type, stent diameter and PCI of a vein graft lesion. Increasing quartiles of predicted benefit-risk difference corresponded with greater overall observed reductions in ischemic events as well as smaller differences in observed bleeding rates between treatment arms at 30 months (see Figure). Conclusions: The magnitude of expected benefit vs harm with continued DAPT beyond 12 months after PCI varies broadly among patients. A small number of variables can be used to identify patients with the greatest anticipated benefit vs harm from long-term DAPT.
Author Disclosures: R.W. Yeh: Consultant/Advisory Board; Modest; Abbott Vascular, Boston Scientific. Employment; Significant; Harvard Clinical Research Institute. Other Research Support; Significant; Merck. E. Secemsky: None. D.J. Kereiakes: Consultant/Advisory Board; Significant; Boston Scientific, Abbott Vascular. A. Gershlick: Consultant/Advisory Board; Modest; Medtronic Corp, Abbott Vascular, Boston Scientific, Astra Zeneca, Eli Lilly, Daiichi Sankyo. Other; Modest; Medtronic Corp, Abbott Vascular, Boston Scientific, Astra Zeneca, Eli Lilly, Daiichi Sankyo. D.J. Cohen: Research Grant; Significant; Eli Lilly, Astra Zeneca, Daiichi Sankyo, Medtronic, Abbott Vascular, Boston Scientific. Honoraria; Modest; Astra Zeneca. Consultant/Advisory Board; Modest; Eli Lilly, Astra Zeneca, Medtronic, Abbott Vascular. J.A. Spertus: Research Grant; Significant; Eli Lilly. Ownership Interest; Significant; Health Outcomes Sciences. P.G. Steg: Research Grant; Significant; Sanofi, Servier. Ownership Interest; Modest; Aterovax. Other; Modest; Amarin, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CSL-Behring, Daiichi-Sankyo, Lilly, Merck Sharpe Dohme, Janssen, Novartis, Medtronic, Pfizer, The Medicines Company, GlaxoSmithKline. Other; Significant; Astra Zeneca, Sanofi, Servier. D.E. Cutlip: Research Grant; Modest; Medtronic, Boston Scientific, Abbott Vascular, Celonova. Consultant/Advisory Board; Modest; Celonova. P.K. Apruzzese: None. J.M. Massaro: Employment; Significant; Harvard Clinical Research Institute. L. Mauri: Research Grant; Modest; Boston Scientific, Abbott, Biotronik. Honoraria; Modest; sanofi, Daiichi Sankyo, Astra Zeneca. Consultant/Advisory Board; Modest; St. Jude, Recor, Svelte.
20265 Angina and Quality of Life Following PCI With Incomplete Revascularization: Results From the Ranolazine for Incomplete Vessel Revascularization (RIVER-PCI) Trial
Karen P Alexander1, Kristi Prather1, Kevin J Anstrom2, Daniel Mark1, Ori Ben-Yehuda3, Linda Davidson-Ray1, Giora Weisz4, Ramin Farzaneh-Far5, Gregg Stone6, E. Magnus Ohman1; 1Cardiology, Duke Univ, Duke Clinical Rsch Institute, Durham, NC, 2Biostatistics, Duke Clinical Rsch Institute, Durham, NC, 3Cardiology, Cardiovascular Rsch Foundation, New York, NY, 4Cardiology, Shaare Zedek Med Cntr, Jerusalem, Israel 5Cardiology, Gilead Sciences, Inc, Durham, NC, 6Cardiology/Columbia Univ, Cardiovascular Rsch Foundation, New York, NY,
Aims: Angina pectoris persists in up to 20% of patients following percutaneous coronary intervention (PCI). Incomplete revascularization may increase this risk for recurrent symptoms and worse health status. Adjunctive pharmacotherapy with ranolazine, an inhibitor of the late sodium current with anti-ischemic properties, may be effective in reducing angina and improving quality of life in patients with incomplete revascularization after PCI. Methods and Results: RIVER-PCI randomized 2,651 subjects with a history of angina and incomplete revascularization after PCI to ranolazine or placebo, with a primary composite endpoint of ischemia-driven hospitalization or revascularization during 1 year or longer follow-up. Secondary quality of life (QOL) outcomes include Seattle Angina Questionnaire (SAQ) angina frequency (AF) and angina treatment satisfaction (TS) scales; and the Duke Activity Status Index (DASI), which were assessed at baseline, 1 month, 6 months, and 12 months. The QOL analysis population included 2,389 subjects (20% female; age 63 ±10.2 years). Baseline SAQ AF was 68.5 ± 24.3, SAQ TS was 83.9 ± 17.1, and DASI was 18.7±14.6. QOL follow up data was available in 96%. Quality of life analyses will be performed as intention-to-treat using a repeated-measures mixed model adjusted for baseline score, ACS indication for index PCI, and history of diabetes mellitus (DM). Pre-specified subgroups include age, sex, DM, heart failure, weekly angina at baseline, and indication for index PCI (ACS vs non-ACS). Multiple imputation to account for missing data and sensitivity analyses for death as lowest value will be performed. Conclusions: The ability of ranolazine to reduce angina and improve quality of life in the long-term medical management of patients with incomplete revascularization post-PCI will be reported overall, and among key subgroups of interest.
Author Disclosures: K.P. Alexander: Research Grant; Modest; Gilead Sciences. K. Prather: None. K.J. Anstrom: None. D. Mark: Research Grant; Modest; Gilead Sciences. Consultant/Advisory Board; Modest; Gilead Sciences. O. Ben-Yehuda: Research Grant; Modest; Gilead Sciences. L. Davidson-Ray: None. G. Weisz: None. R. Farzaneh-Far: Employment; Significant; Gilead Sciences, Inc. G. Stone: None. E. Ohman: Research Grant; Modest; Gilead Sciences. Consultant/Advisory Board; Modest; Gilead Sciences.
Key Words: Percutaneous coronary intervention (PCI), Symptom management
Heart Failure and Cardiomyopathies
Novel Therapies for Common Problems
20304 One Year Follow-up Results From AUGMENT-HF: A Multicenter Randomized Controlled Clinical Trial of the Efficacy of Left Ventricular Augmentation With Algisyl-LVR in the Treatment of Heart Failure
Douglas L Mann1, Stefan D Anker2, Andrew Coats3, Maurizio Volterrani4, Hani N Sabbah5, Robert Dowling6, Randall J Lee7, Andy Hinson8; 1Cardiology, Washington Univ Sch of Med, Barnes Jewish Hosp, St Louis, MO, 2Dept of Innovative Clinical Trials, Univ Med Cntr Göttingen, Göttingen, Germany 3Deans Office, Monash Univ, Melbourne, Australia 4Cardiology, IRCCS San Raffaele Pisana, Rome, Italy 5Cardiovascular Rsch, Henry Ford Health System, Detroit, MI, 6Rsch, Dowling Consulting, Inc., Louisville, KY, 7Div of Cardiology, UCSF, San Francisco, CA, 8R&D, LoneStar Heart, Inc, Laguna Hills, CA,
Background: Therapeutic options for patients with advanced HF are quite limited. The AUGMENT-HF randomized, controlled study tested the hypothesis that LV augmentation with Algisyl (injectable Calcium-Alginate hydrogel) is superior to standard medical therapy (SMT) for treatment of patients with moderate to severe HF. Results were previously reported for the 6 month primary endpoint analysis. This report presents the results from 1 year of extended follow up for this clinical study. Hypothesis: Algisyl LVR is superior to standard medical therapy in the management of chronic HF with a reduced ejection fraction (EF) secondary to ischemic or non-ischemic etiologies. Methods: AUGMENT-HF is an international, multi-centre, prospective, randomized, controlled evaluation of Algisyl-LVR in patients with advanced heart failure (HF). Patients inclusion criteria were LVEF ≤ 35%, peak VO2 of 9.0-14.5 mL/min/kg and LVEDDi 30-40 mm/m2 (LVEDD/BSA). Patients must have been on stable, evidence-based therapy for HF. Results: A total of 58 patients completed the 12 month follow-up. Patients were mean age 62.3 ± 9.6 with ischemic (57.7%) or non-ischemic (42.3%) HF, a mean EF of 25.8 ± 5.5, and symptomatic HF (81% NYHA class III or IV) with a mean Peak VO2 of 12.2 ± 1.8 ml/min/kg, and a mean 6 MWT distance of 293.6 ± 81.3 m. Treatment with Algisyl was associated with improved peak VO2 at 12 months with a treatment effect vs. Control of +2.10 mL/kg/min (95% confidence interval 0.96-3.24, P<0.001). Statistically significant improvements vs. Control at 12 months were observed for VO2 at Anaerobic Threshold (p<0.001), Peak Watts (p=0.003), Total Exercise Time (p=0.002), 6MWT distance (p<0.001), NYHA functional class (p<0.001) and Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical (p=0.018) and Overall (p=0.016) scores. Conclusions: Prior clinical results for Algisyl demonstrated both safety and potentially important clinical benefits for patient with advanced heart failure refractory to SMT. These results demonstrate that Algisyl in addition to standard medical therapy was more effective than standard medical therapy alone for providing sustained 1-year benefits in exercise capacity, symptoms and clinical status for patients with advanced chronic HF.
Author Disclosures: D.L. Mann: Consultant/Advisory Board; Modest; Scientific Advisory Board. S.D. Anker: Consultant/Advisory Board; Modest; Scientific Advisory Board. A. Coats: Consultant/Advisory Board; Modest; Scientific Advisory Board. M. Volterrani: Research Grant; Modest; research grants. H.N. Sabbah: Consultant/Advisory Board; Modest; Scientific Advisory Board. R. Dowling: Consultant/Advisory Board; Modest; Scientific Advisory Board. R.J. Lee: Consultant/Advisory Board; Modest; Scientific Advisory Board. A. Hinson: Employment; Modest; LoneStar Heart.
Key Words: Heart failure, Clinical trials
17797 The-First-in-Man Randomized Trial of a β3-adrenoceptor Agonist in Chronic Heart Failure - the BEAT-HF Trial
Henning Bundgaard1, Anna Axelsson1, Kasper Iversen2, Jakob H Thomsen1, Mathias Sørgaard1, Klaus Kofoed1, Nana V Køber3, Henry Krum4, Søren Boesgaard1, Finn Gustafsson1, Lars Køber1, Helge H Rasmussen5; 1Dept of Cardiology, B 2141, National Univ Hosp, Rigshospitalet, Copenhagen, Denmark 2Dept of Cardiology, Herlev Hosp, Herlev, Copenhagen, Denmark 3Dept of Cardiology, Bispibejerg Hosp, Copenhagen, Denmark 4Dept of Cardiology, Monash Univ’s Cntr of Cardiovascular Rsch and Education in Therapeutics, Monash Med Sch Building, The Alfred Hosp,, Melbourne, Australia 5Dept of Cardiology, Royal North Shore Hosp, Univ of Sydney, Sydney, Australia
Background: Cardiac myocyte Na+ overload is important in the pathogenesis of heart failure (HF) and evidence-based treatments facilitate Na+-K+ pump-mediated Na+-export. Since the nitric oxide synthase-coupled β3 adrenoceptor (β3AR) mediates cardiac myocyte Na+-K+ pump stimulation, we hypothesised that β3AR agonists might be beneficial in HF. In support of this, treatment with β3AR agonists improves clinically relevant indices in sheep and rabbit models of HF. Objective: BEta 3 Agonists Treatment in HF (BEAT-HF) is a randomized, double-blind, placebo-controlled study on effects of the β3AR agonist, Mirabegron (Astellas Pharma, approved for treatment of overactive bladder) in patients with chronic HF. The primary endpoint is increase in left ventricular ejection fraction (LVEF). Secondary endpoints include changes in NT proBNP, left atrial and LV volumes, QT interval and 6-min walking distance, VO2 max and improvement in quality of life. Methods: The study is designed to include 70 patients to detect a difference in LVEF of 4% with a power of 90% and a 2-sided alpha of 5%, allowing for a drop-out rate of 30%. Inclusion criteria are stable HF, NYHA class II-III, LVEF < 40% on ischemic or non-ischemic basis. Patients have to be on optimal pharmacological treatment that must include a β1 AR-blocker. Exclusion criteria include significant valvular disease, renal failure and treatment with digoxin or tricyclic antidepressants. Patients are randomized 1:1 to oral treatment with Mirabegron or placebo for 6 months, starting at 25 mg x 2, doubled weekly to a target dose of 150 mg x 2 or a predefined maximum tolerated dose. LVEF is assessed by cardiac CT. Results: The target number of 70 patients have been randomized and will have completed the 6 months follow-up in September 2015. Patients characteristics; age 58±12 years (mean±SD), 62 (89%) men, 31 (44%) had ischemic cardiomyopathy. The median LVEF at entry was 30% (range 10-39); 66 (94%) were in NYHA Class II and 4 (6%) in Class III. Primary and secondary endpoints will be presented. Conclusions: BEAT-HF is the first-in-man trial to evaluate efficacy of oral treatment with a β3AR agonist in chronic HF. It also explores potential effects on diastolic function, symptoms and repolarisation duration as well as safety (NCT01876433).
Author Disclosures: H. Bundgaard: Speakers Bureau; Modest; Speaker fee from MSD, Sanofi-Avensis, Amgen, AstraZeneca, Pfizer. Other; Significant; Together with University of Sydney, Royal North Shore Hospital and Helge H Rsmussen patented the use of beta 3 adrenoceptor agonists in heart failure.. A. Axelsson: None. K. Iversen: None. J.H. Thomsen: None. M. Sørgaard: None. K. Kofoed: None. N.V. Køber: None. H. Krum: None. S. Boesgaard: None. F. Gustafsson: None. L. Køber: None. H.H. Rasmussen: Other; Significant; Together with University of Sydney, Royal North Shore Hospital and Henning Bundgaard patented the use of beta 3 adrenoceptor agonists in heart failure.
Key Words: Heart failure, Cell signaling, Catecholamines, Beta-adrenergic receptor agonists, Ion transport
20236 Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA): Primary Results of a Randomized, 2 x 2 Factorial, Placebo-Controlled, Double-Blind Clinical Trial
Geeta Gulati1, Siri L Heck1, Pavel Hoffmann2, Anne H Ree3, Jeanette Schulz-Menger4, Florian von Knobelsdorff-Brenkenhoff4, Kjetil Steine1, Åse Bratland5, Berit Gravdehaug6, Helge Røsjø1, Jürgen Geisler3, Torbjørn Omland1; 1Cardiology, Akershus Univ Hosp, Lorenskog, Norway 2Cardiology, Oslo Univ Hosp, Ullevål, Oslo, Norway 3Oncology, Akershus Univ Hosp, Lorenskog, Norway 4Cardiology, Charitè/HELIOS, Berlin, Germany 5Oncology, Oslo Univ Hosp, Norwegian Radium Hosp, Oslo, Norway 6Surgery, Akershus Univ Hosp, Lorenskog, Norway
Introduction: Contemporary adjuvant therapy regimens for early breast cancer are associated with improved survival but at the cost of increased risk of cardiac dysfunction that may progress to clinical heart failure. Preventive neurohormonal blockade may alleviate the decline in cardiac function, but results from randomized, placebo-controlled, double-blind trials are missing. Hypothesis: We tested the hypothesis that cardiotoxicity in patients receiving adjuvant treatment containing anthracyclines with or without trastuzumab and radiation for early breast cancer can be prevented by the concomitant use of the beta-blocker metoprolol and/or angiotensin receptor blocker candesartan. Methods: PRADA (NCT01434134) is a 2x2 factorial, randomized, placebo-controlled, double-blind clinical trial evaluating the cardioprotective effect of metoprolol succinate and/or candesartan cilexetil vs. placebo administered in parallel with adjuvant anti-cancer therapy. The target dose was 100 mg daily for metoprolol and 32 mg daily for candesartan. Between September 2011 and September 2014 126 women (mean age 50.7 years) with early breast cancer and no serious concomitant illness were validly randomized at a single center. The duration of adjuvant therapy ranged from 10 to 61 weeks. The primary endpoint was change in left ventricular ejection fraction (LVEF) as determined by cardiac magnetic resonance imaging (MRI) from baseline to the completion of adjuvant therapy. Results: There was no evidence of an interaction between assignment to candesartan and to metoprolol. In the intention-to-treat analysis, the overall decline in LVEF was 2.6 percentage points (95% confidence interval 1.5 - 3.8) in the placebo group and 0.8 (-0.4 - 1.9) in the candesartan group (p=0.026 for between-group-difference). In the per-protocol analysis the decline was 2.6 (1.4-3.8) percentage points in the placebo group and 0.6 (-0.6-1.8) in the candesartan group (p=0.021 for between-group-difference). No effect of metoprolol on the change in LVEF was observed. Conclusions: Concomitant treatment with candesartan, but not metoprolol provides protection against decline in LVEF in women treated for early breast cancer with adjuvant anti-cancer treatment.
Author Disclosures: G. Gulati: None. S.L. Heck: None. P. Hoffmann: None. A.H. Ree: None. J. Schulz-Menger: Research Grant; Modest; Siemens. Other Research Support; Modest; Siemens, Circle. Consultant/Advisory Board; Modest; Bayer. Other; Modest; SCMR, Vice President, ISMRM , Board Member. F. von Knobelsdorff-Brenkenhoff: None. K. Steine: None. Å. Bratland: None. B. Gravdehaug: None. H. Røsjø: None. J. Geisler: None. T. Omland: Other Research Support; Significant; AstraZeneca, Abbott Diagnostics. Honoraria; Modest; Abbott Diagnostics, Roche Diagnostics. Consultant/Advisory Board; Modest; Novartis.
Key Words: Cardioprotective drugs, Prevention, Cardiac imaging
14228 ANNEXA™-R Part 2: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial Demonstrating Sustained Reversal of Rivaroxaban-Induced Anticoagulation in Older Subjects by Andexanet Alfa (PRT064445), a Universal Antidote for Factor XA (FXA) Inhibitors
Mark Crowther1, Alex Gold2, Genmin Lu3, Janet M Leeds4, Brian L Wiens5, Vandana Marthur6, Janice Castillo7, Pamela B Conley8, Stuart J Connolly9, John T Curnutte10; 1Dept of Pathology & Molecular Medicine; Leo Pharma Chair in Thromboembolism Rsch, McMaster Univ, Hamilton, Canada 2Clinical Development, Portola, South San Francisco, CA, 3Dept of Biology, Portola Pharmaceuticals, Inc, South San Francisco, CA, 4Pharmacology, Portola Pharmaceuticals, Inc, South San Francisco, CA, 5Biometrics, Portola Pharmaceuticals, Inc, South San Francisco, CA, 6Consulting, Mathur Consulting, Woodside, CA, 7Regulatory Affairs, Portola Pharmaceuticals, Inc, South San Francisco, CA, 8Biology, Portola Pharmaceuticals, Inc, South San Francisco, CA, 9Dept of Medicine of the Faculty of Health Sciences, McMaster Univ, Hamilton, Canada 10Rsch & Development, Portola Pharmaceuticals, Inc, South San Francisco, CA,
Background: Direct FXa inhibitors have superior or comparable efficacy and safety relative to warfarin. A specific antidote for these agents is lacking in case of major bleeding or emergent surgery. Andexanet alfa (AnXa) is a modified, recombinant human FXa molecule under development as a specific antidote for FXa inhibitors. We have reported data for Part 1 of the Phase 3 study in older subjects anticoagulated with rivaroxaban, where an AnXa IV bolus reversed anti-FXa activity and restored thrombin generation (TG). Here we report Part 2 data where AnXa was administered as a bolus-plus-infusion (B+I) regimen in a similar population. Data from the phase 3 study in older subjects anticoagulated with apixaban has also been reported demonstrating rapid and sustained reversal of anti-FXa activity and restored TG with AnXa IV bolus or B+I. Aims: To demonstrate immediate and sustained reversal of rivaroxaban anticoagulation following bolus and infusion of AnXa. Methods: ANNEXATM is a 4 part, Phase 3, double-blind, placebo-controlled program comprised of 2 studies of AnXa in older subjects treated with rivaroxaban or apixaban. Part 2 investigated a bolus of AnXa plus a 2-hr infusion. In ANNEXA-R Part 2, 39 subjects age 50 to 75 were randomized to receive AnXa or placebo in a 2:1 ratio. All subjects received rivaroxaban 20 mg PO QD for 4 days to achieve steady state plasma levels. AnXa (800 mg IV bolus plus a 2-hr infusion at 8 mg/min) or placebo was administered on Day 4, 4 hrs after the last rivaroxaban dose (~Cmax). Safety data were collected through Day 43. The primary efficacy endpoint is the percent change from baseline in anti-Xa activity at its nadir between 10 min prior to and 5 min after end of infusion. Additional endpoints included reduction in plasma free fraction of rivaroxaban and restoration of TG. Results: AnXa rapidly reversed the anticoagulant effect of rivaroxaban and sustained it for the duration of the infusion. AnXa was well tolerated. Conclusion: This study continues our investigations of AnXa as an antidote for reversing the anticoagulant effects of rivaroxaban and other FXa inhibitors. Rapid and near complete reversal of the anti-Xa effect of the FXa inhibitors has the potential to improve management of patients with bleeding or those requiring emergent surgery.
Author Disclosures: M. Crowther: Research Grant; Significant; the Heart and Stroke Foundation of Ontario, Leo Pharma. Speakers Bureau; Significant; Leo Pharma, Bayer, Celgene, Shire, CSL Behring. Consultant/Advisory Board; Significant; Janssen, Leo Pharma, Portola, AKP America. A. Gold: Employment; Significant; Portola Pharmaceuticals, Inc. G. Lu: Employment; Significant; Portola Pharmaceuticals, Inc. J.M. Leeds: Employment; Significant; Portola Pharmaceuticals, Inc. B.L. Wiens: Employment; Significant; Portola Pharmaceuticals, Inc. V. Marthur: Consultant/Advisory Board; Significant; Portola Pharmaceuticals, Inc. J. Castillo: Employment; Significant; Portola Pharmaceuticals, Inc. P.B. Conley: Employment; Significant; Portola Pharmaceuticals, Inc. S.J. Connolly: Consultant/Advisory Board; Significant; Portola Pharmaceuticals, Inc. J.T. Curnutte: Employment; Significant; Portola Pharmaceuticals, Inc. Ownership Interest; Significant; 3-V Bionsciences and DiaDexus. Consultant/Advisory Board; Significant; Board of Directors, DiaDexus, Sea Lane Biotechnologies.
Key Words: Factor xa, Anticoagulants, Biomarkers, Anticoagulation
20991 Prevention of Acute Kidney Injury by Nitric Oxide During and After Prolonged Cardiopulmonary Bypass. A Double Blind Randomized Controlled Trial
Chong Lei1, Lorenzo Berra2, Emanuele Rezoagli3, Binglan Yu4, Sabrina Strelow5, Francesco Nordio6, Joseph Bonventre7, Lize Xiong1, Warren Zapol8; 1Anesthesia, Xijing Hosp, Xi'an, China 2?, Massachusetts General Hosp, Harvard Med Sch, Boston, MA, 3Anesthesia, Critical care and Pain Medicine, Massachusetts General Hosp, Harvard Med Sch, Boston, MA, 4Anesthesia Cntr for Critical Care Rsch, Massachusetts General Hosp, Harvard Med Sch, Boston, MA, 5Anesthesia, Massachusetts General Hosp, Boston, MA, 6Medicine, Brigham Women Hosp, Harvard Med Sch, Boston, MA, 7Medicine, Renal Div, Brigham and Women's Hosp, Boston, MA, 8Dept of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hosp, Harvard Med Sch, Boston, MA,
Background: The most common complication associated with prolonged duration cardiopulmonary bypass (CPB) is acute kidney injury (AKI), which markedly increases the mortality rate. Rationale: Prolonged CPB causes hemolysis with high levels of circulating plasma hemoglobin (Hb). Plasma Hb scavenges Nitric Oxide (NO) via the dioxygenation reaction, depleting endogenous NO and causing vasoconstriction, proximal renal tubular injury and AKI. Hypothesis: Exposure to NO during and after CPB protects the kidney, by three possible mechanisms: 1. Selective vasodilation of the pulmonary circulation leading to increased cardiac output and renal perfusion. 2. Reduction of ischemia-reperfusion renal injury and 3. Oxidation of plasma Hb to metHb, which cannot scavenge NO. Study Design: A single center, prospective, randomized, double blind controlled trial comparing treatment with 80 part per million (ppm) NO (NO group) versus N2 (N2 group). Study gas was given via the gas exchanger during CPB and by inhalation for 24h post-operatively in adults. Study Population: 217 consenting adults with normal kidney function undergoing elective multiple valve replacement surgery with CPB. Study Objective: To determine whether NO reduces AKI (primary outcome), and other major complications immediately post-surgery, at 30 days, and 90 days (secondary outcomes). AKI was defined as either an increase of serum creatinine by 50% within 7 days after surgery, or an increase of serum creatinine by 0.3 mg/dl within 48 hrs. Preliminary results: are summarized in the tables 1, 2, 3 and 4. Conclusions: I) Administration of 80ppm NO for 24 hours was safe. Blood metHb was always below 10%. II) NO decreased the incidence of AKI from 63% to 50% (p=0.04, primary endpoint achieved).
Author Disclosures: C. Lei: None. L. Berra: None. E. Rezoagli: None. B. Yu: None. S. Strelow: None. F. Nordio: None. J. Bonventre: None. L. Xiong: None. W. Zapol: Other; Significant; Received NO Royalties.
13496 A Randomized, Placebo Controlled Trial of Late Na Channel Inhibition (ranolazine) in Coronary Microvascular Dysfunction (CMD): Impact on Angina and Myocardial Ischemia
Noel C Bairey-Merz1, Eileen Handberg2, Chrisandra Shufelt1, Puja Mehta1, Margo Minissian1, Louise Thomson3, Daniel Berman3, Leslee Shaw4, Andre Rogatko5, Carl Pepine6; 1Heart Institute, Cedars-Sinai Heart Institute, Los Angeles, CA, 2Cardiology, Univ of Florida, Gainesville, FL, 3Heart Institute, Cedars-Sinai Med Cntr, Los Angeles, CA, 4Cardiology, Emory Univ Sch of Medicine, Atlanta, CA, 5Cancer, Cedars-Sinai Med Cntr, Los Angeles, CA, 6Cardiology, Univ of Florida, Gainesville, CA,
Background: Patients with persistent symptoms and signs of myocardial ischemia and no obstructive coronary artery disease (CAD) often have coronary microvascular dysfunction (CMD), evidenced by limited coronary flow reserve (CFR) on invasive coronary testing and abnormal stress myocardial perfusion reserve on cardiac magnetic resonance imaging (CMRI). Because the mechanistic basis for this syndrome is unclear and outcome trials are lacking, there is no recognized standard of care for such patients. We tested the hypothesis that myocardial ischemia is a mechanistic pathway for angina in CMD using late-Na channel inhibition (ranolazine). Methods: We conducted a randomized, double-blinded, placebo-controlled, cross-over trial of oral ranolazine 500-1,000 mg twice daily for 2 weeks in women and men with symptoms and signs of myocardial ischemia, no obstructive CAD, and abnormal CFR or CMRI myocardial perfusion reserve index (MPRI). The outcomes are angina (Seattle Angina Questionnaire [SAQ]) and angina frequency measured by diary (primary), MPRI and diastolic function on CMRI (secondary), and SAQ score change is related to myocardial perfusion change. The Women’s Ischemia Syndrome Evaluation (WISE) Coronary Angiography and CMRI core laboratories qualified and analyzed the measures. Results: Between March 22, 2011 and April 20, 2015, 435 subjects were screened, 136 (91% women) were enrolled, randomized, and are in follow-up. Baseline data show a mean age 54±12 yrs, 18% diabetes, 54% hypertension, 6% current smoking, body mass index (BMI) of 29±7. The final patient will complete follow-up and data analysis will be concluded by July 30, 2015. The following data will be presented: safety data, efficacy data, SAQ domains (subscale and summary scores), angina diaries, and CMRI variables (global, mid-ventricular and subendocardial MPRI, diastolic function). Conclusions: This trial is the first test of the hypothesis that myocardial ischemia is a mechanistic pathway for angina in CMD subjects in the absence of obstructive CAD using late-Na channel inhibition. The results will provide the needed information for design and implementation of a large, definitive outcome trial to improve the morbidity and mortality of patients with CMD.
Author Disclosures: N.C. Bairey-Merz: Research Grant; Modest; Microvascular, Normal Control. Research Grant; Significant; WISE CVD, Gilead RWISE, FAMRI. Speakers Bureau; Modest; Practice Point Commnications, Pri-Med, Vox Media. Honoraria; Modest; AACE, ACC-AZ Chapter, Florida Hospital, Mayo Scottsdale, Mayo Cancun, NAMS, VBWG, UCLA, U of Chicago, Northwestern, Radcliffe Institute, UCSF. Consultant/Advisory Board; Modest; Amgen, Gilead, Medscape, Pfizer, Scripps. E. Handberg: Other; Modest; Amarin educational grant, Cytori educational grant, Esperion educational grant, Gilead educational grant, ISIS pharmaceuticals educational grant, Mesoblast, Neostem educational grant, United therapeutics educational grant. Other; Significant; Amarin educational grant, Astra Zeneca educational grant, Baxter educational grant, Boehringer Ingleheim educational grant, Catadasis educational grant, Daiichi Sankyo educational grant, Genentech educational grant, Sanofi Aventis educational grant. C. Shufelt: Research Grant; Significant; Gilead RWISE. P. Mehta: Research Grant; Significant; Gilead RWISE, General Electric. M. Minissian: Research Grant; Modest; NIH, AHA, National Lipid Foundation, Gilead. Honoraria; Modest; Preventive Cardiovascular Nurses Assocation, Web MD, Sanofi Aventis-Regeneron. L. Thomson: Research Grant; Significant; NHLBI WISE. D. Berman: None. L. Shaw: Research Grant; Significant; Gilead. A. Rogatko: None. C. Pepine: Research Grant; Modest; Amorcyte Neostem, Cytori, InfraReDx. Research Grant; Significant; AHA, Astra Zeneca, Baxter, Brigham & Women's Hospital, Capricorn, Fujisawa Healthcare Inc, Gilead Sciences Inc., Ikaria Development Subsidiary One LLC, inVentive Health Clinical LLC, Park- Davis, Pfizer, Sanofi Aventis. Honoraria; Modest; Lilly/Cleveland Clinic, Medtelligence. Consultant/Advisory Board; Modest; NHLBI DSMB Chair Freedom Trial, NHLBI Study Section for Progenitor Cell Biology Consortium, NIH/NHLBI.
Key Words: Ischemic heart disease, Magnetic resonance imaging
23226 ALN-PCSsc, an RNAi Investigational Agent That Inhibits PCSK9 With Potential for Effective Quarterly or Possibly Bi-Annual Dosing: Results of Single-Blind, Placebo-Controlled, Phase 1 Single-Ascending Dose (SAD), and Multi-Dose (MD) Trial in Adults With Elevated LDL-C, on and off Statins
Kevin Fitzgerald1, Amy Simon2, Suellen White3, Anna Borodovsky1, Nirav Patel4, Brian Bettencourt5, Valerie Clausen6, Jay D Horton7, Peter Wijngaard8, Robert Kauffman9, David Kallend10; 1Rsch, Alnylam Pharmaceuticals, Cambridge, MA, 2Cliniical Development, Alnylam Pharmaceuticals, Cambridge, MA, 3Clinical Operations, Alnylam Pharmaceuticals, Cambridge, MA, 4Regulatory Affairs, Alnylam Pharmaceuticals, Cambridge, MA, 5Biometrics, Alnylam Pharmaceuticals, Cambridge, MA, 6Drug Safety & Metabolism, Alnylam Pharmaceuticals, Cambridge, MA, 7Internal Medicine, Molecular Genetics, Univ of Texas Southwestern, Dallas, TX, 8Global Innovation Group, The Medicines Company, Parsippany, NJ, 9Consultant, Alnylam Pharmaceuticals, Cambridge, MA, 10Clinical, The Medicines Company, Parsippany, NJ,
Background: ALN-PCSsc is a subcutaneously (sc) delivered RNAi investigational agent that inhibits synthesis of PCSK9 in liver. We previously presented interim data demonstrating up to 94% maximal knockdown of PCSK9 and up to 83% maximal reduction of LDL-C, with mean maximal LDL-C reduction up to 64%. Methods: Individuals were randomized to a single-blind, placebo-controlled, single-ascending dose and multiple dose Phase 1 study to evaluate the safety, pharmacokinetics and pharmacodynamics of sc administered ALN-PCSsc in subjects with elevated LDL-C on and off statins. The primary endpoint was safety and tolerability; secondary endpoints were plasma PK, PCSK9 knockdown, and LDL-C; exploratory endpoints included total cholesterol, HDL-C, VLDL, triglycerides, and Lp(a). Results: A total of 69 subjects were enrolled, with a mean baseline LDL-C =146 mg/dl. 24 subjects were enrolled in 5 SAD cohorts and received placebo (N=6) or drug at fixed doses ranging from 25 mg to 800 mg (N=3-6), per group. 45 subjects were enrolled in 6 MD cohorts, and received: placebo (N=12); 4 doses of 125 mg-qW (N=6); or 2 doses respectively of 250 mg-q2W (N=6); 300 mg-qM (N=6); 300 mg-qM with statin (N=4); 500 mg-qM (N=6); and 500 mg-qM with statin (N=5). ALN-PCSsc was generally well-tolerated; all treatment-emergent adverse events were mild or moderate in severity. No serious adverse events or discontinuations due to adverse events occurred. Here we report safety and efficacy data (out to 180 days) that support the potential for a robust LDL-C lowering (up to a 83% maximal LDL-C reduction, with 44% mean LDL-C reductions remaining 140 days post a single dose) demonstrating the potential for quarterly or possibly bi-annual dosing. In addition, we report for the first time changes in lipoprotein profiles including total cholesterol, HDL-C, non-HDL-c, ApoB, and Lp(a). Conclusion: Our results suggest that an investigational RNAi therapeutic targeting PCSK9 can provide a differentiated approach for the treatment of hypercholesterolemia. ALN-PCSsc was generally well-tolerated, resulted in LDL-C lowering to levels similar to those published for PCSK9 monoclonal antibodies, with an extensive duration of action supportive of effective quarterly or possibly bi-annual dosing.
Author Disclosures: K. Fitzgerald: Employment; Significant; Alnylam Pharmaceuticals. A. Simon: Employment; Significant; Alnylam Pharmaceuticals. S. White: Employment; Significant; Alnylam Pharmaceuticals. A. Borodovsky: Employment; Significant; Alnylam Pharmaceuticals. N. Patel: Employment; Significant; Alnylam Pharmaceuticals. B. Bettencourt: Employment; Significant; Alnylam Pharmaceuticals. V. Clausen: Employment; Significant; Alnylam Pharmaceuticals. J.D. Horton: None. P. Wijngaard: Employment; Significant; The Medicines Company. R. Kauffman: Employment; Significant; Alnylam Pharmaceuticals. D. Kallend: Employment; Significant; The Medicines Company.
Key Words: Hyperlipidemia, Cardiovascular therapeutics, PCSK9, LDL
Hypertension and Vascular Medicine
SPRINT Trial Results: Latest News in Hypertension Management
23696 Systolic Blood Pressure Intervention Trial (SPRINT)
Paul K Whelton; Epidemology, Tulane Univ, New Orleans, LA, Reduction in cardiovascular events and all-cause mortality with intensive blood pressure control: Main results of the Systolic Blood Pressure Interventional Trial (SPRINT). Paul K. Whelton, MB, MD, MSc for the SPRINT Study Research Group. Tulane University Health Sciences Center, New Orleans, LA, USA.
Background: The optimal target for blood pressure (BP) reduction during treatment of patients with hypertension is uncertain. Methods: Adults ≥50 years old with hypertension and at least one additional risk factor for cardiovascular disease (CVD), but excluding persons with diabetes mellitus, prior stroke, or advanced chronic kidney disease (CKD) were randomly assigned to intensive therapy (intensive), targeting a systolic BP (SBP) <120 mm Hg, or standard therapy (standard), targeting a systolic BP <140 mm Hg. The primary outcome was a composite of first occurrence of myocardial infarction, acute coronary syndrome, stroke, heart failure, or cardiovascular disease death. (ClinicalTrials.gov, NCT01206062) Results: The study sample encompassed a diverse group of 9,361 volunteers with an average age of 67.9 years. Pre-specified subgroups comprising persons with CKD (28.5%), history of CVD (20.1%), or ≥75 years old (28.2%) were enrolled. The intervention successfully yielded a sustained difference in SBP between the intensive and standard groups. The SPRINT intervention was stopped early due to beneficial results, with an approximately 30% reduction in the primary outcome and 25% reduction in all-cause mortality in the intensive compared to standard group. Similar results were identified across pre-specified subgroups defined by age, gender, race, presence of CVD, SBP tertiles and renal function. Some expected adverse effects were more common in the intensive group. Conclusions: In older adults with hypertension who are at risk for CVD, targeting a SBP lower than recommended in current treatment guidelines results in a substantial reduction in CVD events and all-cause mortality compared to standard therapy.
Author Disclosures: P.K. Whelton: None.
Key Words: Hypertension, Blood pressure, Clinical trials, Prevention, Antihypertensive agents
Intervention and Surgery
Two Year Clinical Update: CT Surgery Network Severe MR Trial
23690 Two-Year Outcomes following Mitral Valve Repair or Replacement for Severe Ischemic Mitral Regurgitation
Daniel Goldstein1, Gorav Ailawadi2, Alan Moskowitz3, Louis P Perrault4, Michael Parides3, Annetine Gelijns3, Judy Hung5, Francois Dagenais6, A. Marc Goldfarb7, Vinod Thourani8, Michael Argenziano9, James Gammie10, Michael Mack11, Philippe Demers4, Pavan Atluri12, Eric A Rose3, Karen O'Sullivan13, Deborah Williams3, Emilia Bagiella13, Robert Michler14, Richard Weisel15, Marissa Miller16, Wendy C Taddei-Peters17, Peter K Smith18, Ellen Moquete3, Patrick O'Gara19, Jessica R Overbey3, Irving Kron2, Michael A Acker12, CTSN Investigators; 1Cardiothoracic Surgery, Montefiore Med Cntr, Bronx, NY, 2Cardiothoracic Surgery, Univ of Virginia Health System, Charlottesville, VA, 3Population Health Science and Policy, Icahn Sch of Medicine at Mount Sinai, New York, NY, 4Surgery, Montreal Heart Institute, Montreal, Canada 5Cardiology, Massachusetts General Hosp, Boston, MA, 6Cardiothoracic Surgery, Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Quebec, Canada 7Thoracic & Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH, 8Cardiothoracic Surgery, Emory Univ Hosp Midtown, Atlanta, GA, 9Cardiac Surgery, NewYork-Presbyterian Hosp/Columbia Univ Med Cntr, New York, NY, 10Cardiac Surgery, Univ of Maryland, Baltimore, MD, 11Cardiovascular Medicine, Baylor Rsch Institute, Plano, TX, 12Cardiovascular Surgery, Univ of Pennsylvania Health System, Philadelphia, PA, 13Health Evidence and Policy, Icahn Sch of Medicine at Mount Sinai, New York, NY, 14Cardiothoracic Surgery, Montefiore-Einstein Heart Cntr, Bronx, NY, 15Cardiovascular Surgery, Toronto General Hosp, Toronto, Canada 16Cardiovascular Sciences, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, 17Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, NY, 18Surgery, Duke Univ, Durham, NC, 19Cardiovascular Surgery, Brigham and Women's Hosp, Boston, MA,
Background: The Cardiothoracic Surgical Trials Network recently reported no difference in left ventricular end systolic volume index (LVESVI) at one year post-surgery between patients randomized to mitral repair (n=126) or replacement (n=125) for severe ischemic mitral regurgitation (MR). However, repair patients experienced significantly more recurrent MR than replacement patients. We report the 2-year follow-up of trial participants. Methods: We followed 251 patients randomized to repair or replacement for 2 years. LVESVI was assessed using a Wilcoxon rank sum test in which deaths were assigned the lowest rank. Results: Among surviving patients, mean 2-year LVESVI was 52.6 ±28 mL/m2 in the repair and 60.7±39 mL/m2 in the replacement arm (mean decrease from baseline 9.0 mL/m2 and 6.5 mL/m2, respectively). Two-year mortality was 19.1% for repair and 23.2% for replacement (HR 0.79, 95% CI 0.46-1.35; p=0.39). There was no significant between-group difference in LVESVI after adjustment for death (Z=-1.32, p=0.19). The rate of moderate or severe MR recurrence at 24 months was higher in the repair than replacement arm (36.3% vs.1.3%; p< .0001). In the repair arm, the 2-year LVESVI was 62.5 ± 25 in patients with recurrent MR vs. 47.0 ± 29 in those without MR (p=0.0042). Four repair patients and 1 replacement patient underwent MV reoperation. There was no significant difference in the composite of MACCE, functional status or quality of life at 2 years. Rates (pt-yr) of serious adverse events (1.5 vs.1.3, p=0.18) and overall readmissions (0.8 vs. 0.7, p=0.14) were not different between arms, but repair patients experienced a higher rate of serious heart failure (0.24 vs. 0.15, p=0.049) and more CV readmissions (0.48 vs. 0.33, p=0.02) than replacement patients. Conclusions: We observed no difference in LV reverse remodeling or survival between repair and replacement at two years. Replacement provided more durable correction of MR, as well as fewer HF events and CV readmissions.
Author Disclosures: D. Goldstein: Consultant/Advisory Board; Modest; Heartware Inc, Medtronic Inc. Other; Modest; Thoratec Inc, SunshineHeart Inc. G. Ailawadi: Speakers Bureau; Modest; St. Jude. Consultant/Advisory Board; Modest; Abbott Vascular, Edwards, Atricure. A. Moskowitz: None. L.P. Perrault: None. M. Parides: None. A. Gelijns: None. J. Hung: None. F. Dagenais: None. A. Goldfarb: Speakers Bureau; Significant; Atricure, St. Jude medical, Medtronic, Edwards. Ownership Interest; Significant; ClearFlow. Consultant/Advisory Board; Significant; Abbott, On-x. V. Thourani: None. M. Argenziano: None. J. Gammie: None. M. Mack: Consultant/Advisory Board; Modest; Edwards Lifesciences, Abbott Vascular. P. Demers: None. P. Atluri: None. E.A. Rose: None. K. O’Sullivan: None. D. Williams: None. E. Bagiella: None. R. Michler: None. R. Weisel: None. M. Miller: None. W.C. Taddei-Peters: None. P.K. Smith: None. E. Moquete: None. P. O’Gara: None. J.R. Overbey: None. I. Kron: None. M.A. Acker: None.
Key Words: Cardiac surgery, Mitral regurgitation, Ischemic heart disease
2015 Clinical Science Special Reports Abstracts
Intervention and Surgery
Novel Findings from Next Generation Registries
20289 Increased Incidence of Infective Endocarditis After the 2009 European Society of Cardiology Guideline Update: A Nation-wide Study in the Netherlands
Floris S van den Brink, Martin J Swaans, Arash Alipour, Johannes C Kelder, Wybren Jaarsma, Frank D Eefting, Jurrien M ten Berg; Dept of Cardiology, St. Antonius Ziekenhuis, Nieuwegein, Netherlands
Background: After the introduction of the updated 2007 ACC/AHA infective endocarditis (IE) guideline and the NICE 2008 guideline, the ESC guidelines on Prevention, Diagnosis and Treatment of Infective Endocarditis followed in 2009. Prophylaxis for patients at risk became less strict afterwards. There is limited data on IE trends after the introduction of this ESC guideline. Hypothesis: The ACC/AHA guideline uses virtually similar criteria for prophylaxis as the ESC guideline and has shown a significant rise in IE since its introduction. We hypothesize that the same trend will be observed in the Netherlands. Methods: We performed a nation-wide retrospective trend study using segmented regression analysis of the interrupted time series. The patient data were obtained via the national healthcare insurance database. We compared the data before and after the introduction of the 2009 ESC guideline. Results: Between 2005 and 2011 a total of 5213 patients were hospitalized with IE in the Netherlands. During this period there was a significant increase in infective endocarditis from 30.2 new cases per 1.000.000 in 2005 to 62.9 cases per 1.000.000 in 2011 (p<0.001). Historically more male subjects are affected with IE; 69.9% of the patients were men. The increase in IE was similar in both sexes. In 2009 the incidence of IE increased significantly above the projected historical trend (Rate Ratio: 1.327, 95% CI: 1.205 - 1.462 p<0.001). This coincides with the introduction of the 2009 ESC guideline (see figure 1). Conclusion: This observational study shows that there has been a steady increase in the IE incidence between 2005 and 2011. After the introduction of the 2009 ESC guidelines the incidence increased more than expected from previous historical trends. The male to female ratio in IE is unchanged at a 2:1 ratio and the increase is similar in both groups.
Author Disclosures: F.S. van den Brink: None. M.J. Swaans: None. A. Alipour: None. J.C. Kelder: None. W. Jaarsma: None. F.D. Eefting: None. J.M. ten Berg: None.
Key Words: Endocarditis, Guidelines, Prevention, International
20197 Examining Prevailing Genotype-Phenotype Correlations in Hypertrophic Cardiomyopathy: Findings From The Sarcomeric Human Cardiomyopathy Registry (SHaRe)
Carolyn Y Ho1, Sharlene M Day2, Euan A Ashley3, Michelle Michels4, Alexandre Pereira5, Jonathan Fox6, Colleen Caleshu7, Allison L Cirino1, Steve Colan8, Danielle Wrolstad9, Eric M Green10, Iacopo Olivotto11, SHaRe Investigators; 1Cardiovascular Medicine, Brigham and Women's Hosp, Boston, MA, 2Cardiology, MyoKardia, Ann Arbor, MI, 3Stanford Cntr for Inherited Cardiovascular Disease, Stanford Hosp and Clinics, Palo Alto, CA, 4Cardiology, Erasmus Med Cntr, Rotterdam, Netherlands 5Heart Institute, Univ of Sao Paulo, Sao Paulo, Brazil 6Clinical, MyoKardia, South San Francisco, CA, 7Cntr for Inherited Cardiovascular Disease, Stanford Hosp and Clinics, Palo Alto, CA, 8Cardiology, Boston Children's Hosp, Boston, MA, 9Biostatistics, Biostatistics Consultant, Chisago City, MN, 10Translational Rsch, MyoKardia, South San Francisco, CA, 11Referral Cntr for Cardiomyopathies, Cargo Univ Hosp, Florence, Italy
Introduction: The Sarcomeric Human Cardiomyopathy Registry (SHaRe) was established to amass robust large-scale, longitudinal genotype, phenotype, and outcomes data for HCM. Here we examine prevailing concepts regarding genotype and phenotype in HCM. Methods: Seven HCM centers in the United States, Europe, and Brazil mapped key fields from existing databases to a central database. Genetic testing interpretation was standardized. Two-sample t-test or Fisher’s exact test assessed differences among genotypic subgroups. Composite (EF<55%, ICD shock, Afib, stroke, septal reduction, heart failure, cardiac arrest, death), heart failure, and arrhythmic cardiovascular events were assessed with Kaplan-Meier log-rank tests. Results: Of 4686 HCM patients, 2184 unrelated probands (54%) underwent genetic testing. Of these, 963 probands had pathogenic or likely pathogenic mutations (sarcomere(+)) and 1014 had no mutations (sarcomere(-)). Compared to sarcomere(-), sarcomere(+) probands were 12.4 yrs younger at diagnosis and had earlier development of AFib and composite outcome, as well as heart failure, and arrhythmic outcomes (p<0.001 for all; Figure). Probands with MYH7 mutations were 2.2 yrs younger at diagnosis and had earlier development of AFib and composite outcome than other sarcomere(+). Probands with ≥2 mutations were 6.2 yrs younger at diagnosis reached composite and arrhythmic outcomes earlier than other sarcomere(+). LV wall thickness and outcomes were not significantly different in thin vs thick filament probands. Conclusions: This is the largest clinical study of genotyped HCM patients. Probands with sarcomere mutations, MYH7, and ≥2 mutations have more severe clinical profiles. Continued expansion of this cohort and novel approaches to genotype-phenotype analysis are required to gain further granularity, new insights into the biology of HCM, and to identify better predictors of prognosis.
Author Disclosures: C.Y. Ho: Other Research Support; Significant; MyoKardia. S.M. Day: Other Research Support; Significant; MyoKardia. E.A. Ashley: Ownership Interest; Significant; Co-Founder, Personalis, Inc.. M. Michels: None. A. Pereira: None. J. Fox: Employment; Significant; MyoKardia. Ownership Interest; Significant; MyoKardia. C. Caleshu: Ownership Interest; Modest; Personalis. Consultant/Advisory Board; Modest; Invitae, Gilead, GeneDx, Recombine, Myriad Genetics. A.L. Cirino: Consultant/Advisory Board; Modest; Invitae. S. Colan: Other Research Support; Significant; MyoKardia. D. Wrolstad: Consultant/Advisory Board; Modest; MyoKardia. E.M. Green: Employment; Significant; MyoKardia. Ownership Interest; Modest; Element Science. Ownership Interest; Significant; MyoKardia. I. Olivotto: Other Research Support; Significant; MyoKardia.
Key Words: Hypertrophic cardiomyopathy, Genetics, Follow-up studies, Outcomes
18075 Appropriate Use Criteria for Coronary Revascularization and Trends in Utilization, PatientSelection, and Appropriateness of Percutaneous Coronary Intervention - FindingsFrom the NCDR-CathPCI Registry
Nihar Desai1, Steven Bradley2, Craig Parzynski3, Brahmajee Nallamothu4, Jeremy Ader5, Paul Chan6, Manesh Patel7, John A Spertus8, Harlan Krumholz1, Jeptha Curtis1; 1Cardiovascular Medicine, Yale Sch of Medicine, New Haven, CT, 2Cardiovascular Medicine, Univ of Colorado Sch of Medicine, Denver, CO, 3Medicine, Cntr For Outcomes Rsch and Evaluation, New Haven, CT, 4Cardiovascular Medicine, Univ of Michigan, Ann Arbor, MI, 5Medicine, Yale Sch of Medicine, New Haven, CT, 6Cardiovascular Medicine, Mid America Heart Institute, Kansas City, MO, 7Cardiovascular Medicine, Duke Clinical Rsch Cntr, Durham, NC, 8Cardiovascular Medicine, Mid-America Heart Institute, Kansas City, MO,
Background: While the appropriateness of PCI has received substantial attention and is the focus of national quality improvement campaigns, the impact of the appropriate use criteria (AUC) on patient selection and trends in PCI appropriateness are unknown. Methods: We applied validated algorithms based on the 2012 AUC to examine trends in the appropriateness of all PCIs in the NCDR-CathPCI registry between July 2009 and December 2014 performed at hospitals that participated continuously in the registry during the study period and performed, on average, ≥ 10 non-acute PCIs in each year. We examined changes in clinical and procedural characteristics as well as trends in the proportion of non-acute PCIs considered inappropriate. Results: A total of 2.7 million PCI procedures from 766 hospitals were included in our study cohort. Annual PCI volume for acute indications was consistent over the study period (2010: 377,540; 2014: 374,543), but there was a 34% reduction in the volume for non-acute PCIs (2010: 89,704; 2014: 59,375). Among patients undergoing non-acute PCI, we found marked increases in reported anginal severity, use of anti-anginal medications, and high-risk findings on non-invasive testing (p<0.001 for all) but only modest increases in multivessel CAD found on angiography. The proportion of non-acute PCIs classified as inappropriate declined significantly (26% to 13%, p<0.001) (Figure, left panel). There were similar reductions but persistent variation at the hospital-level (Figure, right panel). Conclusion: From July 2009 to December 2014, there has been a 50% reduction in the proportion of non-acute PCIs considered inappropriate but persistent hospital-level variation. Reductions in non-acute PCI volume coupled with increases in anginal severity, use of anti-anginal medications, and high-risk findings on non-invasive testing may reflect improved patient selection for PCI, improved documentation or potential upcoding of clinical severity.
Author Disclosures: N. Desai: None. S. Bradley: None. C. Parzynski: None. B. Nallamothu: None. J. Ader: None. P. Chan: None. M. Patel: None. J.A. Spertus: Ownership Interest; Significant; Health Outcomes Sciences, Inc.. H. Krumholz: None. J. Curtis: None.
20283 Clopidogrel on Top of Aspirin for the Prevention of New-onset Migraine Headache Attacks Following Transcatheter Closure of Atrial Septal Defects: A Prospective, Randomized, Double Blind Trial (CANOA)
Josep Rodes-Cabau1, Eric Horlick2, Reda Ibrahim3, Asim Cheema4, Marino Labinaz5, Najef Nadeem6, Mark Osten2, Melanie Cote7, Donald Rivest8, Alier Marrero9, Christine Houde10, Josep Ramon Marsal11; 1Cardiology, Quebec Heart & Lung Institute, Quebec City, Canada 2Cardiology, Toronto General Hosp, Toronto, Canada 3Cardiology, Montreal Heart Institute, Montreal, Canada 4Cardiology, St Michael's hospital, Toronto, Canada 5Cardiology, Ottawa Heart Institute, Ottawa, Canada 6Cardiology, Queen Elizabeth II Health Sciences Cntr, Halifax, Canada 7Cardiology, Quebec Heart & Lung Institute, Quebec, Canada 8Neurology, Hotel Dieu de Levis, Levis, Canada 9Neurology, Cntr Hospier Universitaire George L Dumont, Moncton, Canada 10Pediatric Cardiology, Cntr Universitaire Hospier de Quebec, Quebec, Canada 11Epidemiology Unit, USR, Epidemiology Unit, USR, Lleida-Pirineu, Spain
Background: The occurrence of new-onset migraine attacks (MA) is a well-known complication of transcatheter atrial septal defect (ASD) closure. It has been suggested that clopidogrel may reduce MA following ASD closure. The objective of this study was to assess the efficacy of clopidogrel on top of aspirin for the prevention of MA following ASD closure. Methods and Results: This was a prospective, multicenter, randomized, double blind controlled trial. Patients with indication for ASD closure and no prior history of MA were randomized (1:1) to receive dual antiplatelet therapy (DAT, aspirin+clopidogrel) versus single antiplatelet therapy (SAT, aspirin+placebo) for 3 months following ASD closure. The occurrence and severity of MA were evaluated by a structured migraine headache questionnaire (including the Migraine Disability Assessment [MIDAS] test) at 1- and 3-month follow-up in addition to a headache diary. A total of 171 patients (49±15 years, 106 women) were included (87 and 84 in the SAT and DAT groups, respectively). All patients had successful transcatheter ASD closure with the Amplatzer septal occluder device with no major complications. Patients in the DAT group had a lower incidence of MA following ASD closure (21.8% vs. 9.5%, OR: 0.38, 95% CI: 0.15-0.89, P=0.031), and a reduced number of monthly MA days within the 3 months following the procedure (IRR: 0.61, 95% CI: 0.41-0.91, P=0.035). In patients with MA, those in the DAT group had less severe MA as evaluated by the MIDAS test (no patient with moderately or severely disabling MA in the DAT group vs.37% in the SAT group, P=0.046). Conclusions: Clopidogrel on top of aspirin reduced the occurrence and severity of MA following ASD closure. These results suggest the potential role of prothrombotic status on the pathogenesis of migraine in such patients. Clinicaltrials.gov:NCT00799045
Author Disclosures: J. Rodes-Cabau: None. E. Horlick: None. R. Ibrahim: None. A. Cheema: None. M. Labinaz: None. N. Nadeem: None. M. Osten: None. M. Cote: None. D. Rivest: None. A. Marrero: None. C. Houde: None.
Key Words: Adult congenital heart disease, Atrial septal defect
Arrhythmias and Electrophysiology
Cutting Edge Technologies in EP
17658 Cardiac Resynchronization Therapy is Detrimental in Patients With QRS Duration Greater Than 180ms and Right Bundle Branch Block Morphology: Analysis From the Medicare ICD Registry
Varun Sundaram1, Kenneth Bilchick2, Albert L Waldo1, Brigid Wilson3, Yogesh N Reddy4, Jayakumar Sahadevan3; 1Cardiology, Univ Hosps Case Med Cntr, Cleveland, OH, 2Cardiology, Univ of Virginia Health System, Charlottesville, OH, 3Cardiology, Louis Stokes Cleveland Veteran Affairs Med Cntr, Cleveland, OH, 4Cardiology, Mayo Clinic, Rochester, MN,
Background: Benefits of cardiac resynchronization therapy (CRT) in patients with very wide (>180ms) QRS complex duration (QRSD) have not been adequately studied, but current guidelines include this group in the recommendation for CRT. When the QRSD is >180ms, it is likely a combination of electrical dysynchrony and electrical uncoupling. Hypothesis: We hypothesized that patients with very wide QRSD (>180ms) do not benefit from CRT. Methods: We analyzed 14,946 patients from the Medicare Implantable Cardioverter Defibrillator Registry who received CRT-D between January 2005 and April 2006. We classified them into 3 groups based on their QRSD (120-149ms, 150-179ms and >180 ms), and followed for 3 years for clinical outcomes, including death, and a composite of death and heart failure hospitalization. The effect of QRSD on survival was presented as hazard ratios (HR), with QRSD of 150-179 ms with left bundle branch block (LBBB) as the reference. Subgroup analysis was performed based on bundle branch block (BBB) morphology and QRSD. Results: 2,948 of 14,496 patients had QRSD >180ms. After adjustment in a multivariable Cox proportional hazards model, we found that outcomes for patients with a very wide QRSD depended on the underlying BBB morphology. Patients with LBBB or intraventricular conduction delay (IVCD) with very wide QRSD had clinical outcomes which were comparable with the reference group (LBBB with 150-179ms). But patients with right BBB with very wide QRSD had worse clinical outcomes (HR for 1 year mortality=1.80, p <0.001), and, in fact, worse than patients with RBBB and QRSD of 120-149 ms. Conclusions: In this large registry study, outcomes for patients with very wide QRSD depended on underlying BBB morphology. Patients with LBBB and IVCD with very wide QRSD continued to benefit from CRT. However, CRT was detrimental in patients with right BBB and very wide QRSD. These data have implications for guideline recommendations.
Author Disclosures: V. Sundaram: None. K. Bilchick: None. A.L. Waldo: None. B. Wilson: None. Y.N. Reddy: None. J. Sahadevan: None.
Key Words: CRT, Efficacy, Heart failure
20237 Miniaturized Transcatheter Delivered Cardiac Pacing: Primary Results of a Worldwide Clinical Trial
Dwight W Reynolds1, Gabor Z Duray2, Razali Omar3, Kyoko Soejima4, Petr Neuzil5, Shu Zhang6, Calambur Narasimhan7, Clemens Steinwender8, Lluis Mont9, Michael Lloyd10, Paul R Roberts11, Venkata Sagi12, John Hummel13, Maria G Bongiorni14, Reinoud E Knops15, Christopher R Ellis16, Charles C Gornick17, Matthew A Bernabei18, Verla Laager19, Kurt Stromberg19, Eric R Williams19, Philippe Ritter20; 1Cardiovascular Section, Univ of Oklahoma HSC, Oklahoma City, OK, 2Clinical Electrophysiology Dept of Cardiology, Med Cntr, Hungarian Defence Forces, Budapest, Hungary 3Electrophysiology and Pacing Unit, National Heart Institute, Kuala Lumpur, Malaysia 4Dept of Cardiology, Kyorin Univ Hosp, Tokyo, Japan 5Dept of Cardiology, Na Homolce Hosp, Prague, Czech Republic 6Clinical EP Lab and Arrhythmia Cntr, Fuwai Hosp, Beijing, China 7Div of Electrophysiology, Dept of Cardiology, CARE Hosps and CARE Foundation, Hyderabad, India 8Dept of Cardiology, Linz General Hosp, Johannes Kepler Univ Sch of Medicine, Linz, Austria 9Arrhythmia Section, Hosp Clínic, Universitat de Barcelona, Barcelona, Spain 10Emory Heart and Vascular Cntr, Emory Univ Hosp, Atlanta, GA, 11Highfield Campus, Univ of Southampton, Southampton, United Kingdom 12Baptist Heart Specialists, Baptist Heart Specialists, Jacksonville, FL, 13Wexner Med Cntr, The Ohio State Univ, Columbus, OH, 14Cardiology, Azienda Ospedlaiero Universitario, Pisa PI, Italy 15Academisch Medisch Centrum (AMC), Academisch Medisch Centrum (AMC), Amsterdam, Netherlands 16Vanderbilt Heart and Vascular Institute, Vanderbilt Univ Med Cntr, Nashville, TN, 17Minneapolis Heart Institute, Minneapolis Heart Institute, Minneapolis, MN, 18Lancaster Heart and Vascular Institute, Lancaster Heart and Vascular Institute, Lancaster, PA, 19CRHF, Medtronic, plc, Mounds View, MN, 20Dept of Electrophysiology and Cardiac Pacing and, Hosp Haut Leveque, Univ Hosp of Bordeaux, Pessac Cedex, France
Background: For a half century, permanent cardiac pacing for symptomatic bradycardia has been achieved with systems consisting of a subcutaneous electrical generator connected to one or more leads that conduct the pacing therapy to the cardiac tissue. While effective, approximately 1 in 8 patients may experience an early complication, usually related to the lead or pocket. Performance of a novel miniaturized leadless pacemaker was evaluated in the Micra Transcatheter Pacing Study. Design: The prospective single-arm trial was designed to assess the safety and efficacy of the Micra™ Transcatheter Pacing System (TPS, 0.8 cubic centimeters, 2.0 grams). Enrolled patients met Class I or II guideline indications for de novo ventricular pacing and were not restricted by comorbidities. Patients underwent TPS implant attempt from the femoral vein with the device affixed in the right ventricular endocardium by 4 flexible nitinol tines. Prespecified primary objectives were: freedom from system related major complications at 6 months (safety, assumed performance >90%) and demonstration of low and stable pacing capture thresholds at 6 months (efficacy, assumed performance of 89% with threshold ≤2 Volts and no increase of >1.5 Volts relative to implant). Safety and trial conduct oversight are provided by an independent data monitoring committee. Results: Patient recruitment began December 5, 2013 and concluded May 14, 2015 with 744 patients enrolled at 56 centers located in 19 countries spanning North America, Europe, Asia, and Australia. The mean age was 75.7 ± 11.0 years (range 19 - 94 years), 58.4% were male, and mean body mass index was 27.6 ± 5.3 (range 14 - 57). Most (94%) patients had one or more comorbidity, including hypertension (78.4%), atrial tachyarrhythmia (75.1%), vascular disease (41.0%), and chronic lung disease (29.0%). TPS was successfully implanted in 719 of 725 attempts (99.2%). Average follow-up duration was 4.4 ± 3.2 months. Primary: endpoint analysis will be performed and reviewed by the data monitoring committee July 18, 2015 with results available for the AHA presentation. Conclusion: Performance of the Micra TPS has been evaluated through a large worldwide clinical trial. The potential implications for this novel technology will be discussed.
Author Disclosures: D.W. Reynolds: Research Grant; Significant; Medtronic, Biotronik. Speakers Bureau; Significant; Medtronic, Sorin Group. Consultant/Advisory Board; Significant; Medtronic. G.Z. Duray: Research Grant; Modest; Medtronic, St. Jude Medical, Biotronik. Speakers Bureau; Modest; Medtronic, St. Jude Medical, Biotronik. Honoraria; Modest; Medtronic, St. Jude Medical, Biotronik. Consultant/Advisory Board; Modest; Medtronic, St. Jude Medical, Biotronik. R. Omar: Speakers Bureau; Modest; Medtronic. Honoraria; Modest; Medtronic. Consultant/Advisory Board; Modest; Medtronic, Boston Scientific, Biotronik. K. Soejima: Research Grant; Modest; Boehringer Ingelheim. Speakers Bureau; Modest; Medtronic Japan, St. Jude Medical Japan. Honoraria; Modest; Boehringer Ingelheim. Consultant/Advisory Board; Modest; Boston Scientific Japan. P. Neuzil: None. S. Zhang: Honoraria; Modest; Medtronic. C. Narasimhan: None. C. Steinwender: Honoraria; Modest; Medtornic. Consultant/Advisory Board; Modest; Medtronic. L. Mont: Speakers Bureau; Modest; Medtronic, St. Jude Medical, Biotronik, Boston Scientific, Sorin Group, Biosense Webster. Consultant/Advisory Board; Modest; Medtronic, St. Jude Medical, Biotronik, Boston Scientific, Sorin Group, Biosense Webster. M. Lloyd: Honoraria; Modest; Medtronic. Consultant/Advisory Board; Modest; Medtronic. P.R. Roberts: Research Grant; Modest; Medtronic. Honoraria; Modest; Medtronic. Consultant/Advisory Board; Modest; Medtronic, Boston Scientific. V. Sagi: None. J. Hummel: Research Grant; Modest; Medtronic. Consultant/Advisory Board; Modest; Medtronic. M.G. Bongiorni: Research Grant; Modest; Medtronic, Quintiles, St. Jude Medical, Boston Scientific, Biosense Webster. Honoraria; Modest; Biosense Webster, Boston Scientific. Consultant/Advisory Board; Modest; Spectranetics. R.E. Knops: Research Grant; Significant; St. Jude Medical, Boston Scientific, Medtronic. Speakers Bureau; Modest; St. Jude Medical, Boston Scientific, Biotronik. C.R. Ellis: Honoraria; Modest; Spectranetics. Consultant/Advisory Board; Modest; Atricure, Sentre Heart, Boston Scientific. Other; Significant; Atricure, Boston Scientific, Thoractec, Boehringer Ingelheim, Heart Ware, Medtronic. C.C. Gornick: None. M.A. Bernabei: None. V. Laager: Employment; Significant; Medtronic. K. Stromberg: Employment; Significant; Medtronic. E.R. Williams: Employment; Significant; Medtronic. P. Ritter: Consultant/Advisory Board; Significant; Medtronic.
Key Words: Pacemakers, Device, Pacing
18002 A Randomized Controlled Trial of a Video Decision Support Tool to Depict Goals of Care and Resuscitation Options for Patients With Advanced Heart Failure
Areej El-Jawahri1, Michael Paasche-Orlow2, Daniel Matlock3, Lynne Stevenson4, Eldrin Lewis4, Garrick Stewart4, Yuchiao Chiang1, Marc Semigran1, Beth Walker-Corkery1, Kimberly Parks1, Hacho Bohossian5, Henry Ooi6, Eileen Mann1, Angelo Volandes1; 1Medicine, Massachusetts General Hosp, Boston, MA, 2Medicine, Boston Med Cntr, Boston, MA, 3Medicine, Univ of Colorado, Denver, CO, 4Medicine, Brigham and Women's Hosp, Boston, MA, 5Medicine, Newton-Wellesley Hosp, Newton, MA, 6Medicine, Vanderbilt Univ, Nashville, TN,
Background: Core aspects of advance care planning for people with advanced heart failure (HF), such as decisions about goals of care and CPR/intubation, are challenging to present. This study examined the impact of a video decision tool on decisions regarding goals of care and CPR/intubation. Methods: A 6 site RCT of 246 pts > 64 yrs with advanced HF and estimated >50% likelihood of 2 year mortality. Controls received a verbal description of the goals of care (life-prolonging care, limited care, and comfort care) and CPR/intubation. Video intervention participants received the same verbal description plus a 6-minute video depicting the 3 levels of care and CPR/intubation on a mannequin. The primary analysis compared the proportion of patients preferring comfort care to either life-prolonging or limited care after the intervention. Secondary outcomes were CPR/intubation preferences, knowledge of options (5-item test, range 0-5), and comfort viewing the video. Results: Immediately after hearing the verbal description in the control group, 37 (30%) chose comfort, 27 (22%) chose limited, 50 (41%) chose life-prolonging, and eight (7%) were uncertain. Immediately after hearing the verbal description and watching the video in the intervention group, 63 (51%) chose comfort, 31 (25%) chose limited, 27 (22%) chose life-prolonging, and two (2%) were uncertain (P=0.0004). Video participants (vs. controls) were less likely to want CPR (31% vs. 59%, P <0.0001) and intubation (20% vs. 46%, P <0.0001), and had higher mean knowledge scores (4.1 vs. 3.0; P < 0.0001). Patients were comfortable viewing the video (99%) and would recommend it to others (97%). Conclusions: Patients who viewed a video about goals of care and CPR/intubation were more likely to select a focus on comfort and less likely to desire CPR/intubation compared to patients receiving verbal information only. Patients were comfortable viewing the video, and demonstrated better knowledge about their options.
Author Disclosures: A. El-Jawahri: None. M. Paasche-Orlow: None. D. Matlock: None. L. Stevenson: None. E. Lewis: Consultant/Advisory Board; Modest; Novartis. Research Grant; Significant; Novartis, Amgen, Sanofi. G. Stewart: None. Y. Chiang: None. M. Semigran: None. B. Walker-Corkery: None. K. Parks: None. H. Bohossian: None. H. Ooi: None. E. Mann: None. A. Volandes: None.
Key Words: Cardiopulmonary resuscitation, Quality of medical care, Patient education/teaching psychosocial aspects
20235 Peri-procedural Safety of Left Atrial Appendage Occlusion With the WATCHMAN Device. Preliminary Data From the EWOLUTION Registry
Lucas Boersma1, Tim Betts2, Horst Sievert3, Boris Schmidt4, Emmanuel Teiger5, Corrado Tamburino6, Martin W. Bergmann7; 1Cardiology, St.Antonius Hosp, Nieuwegein, Netherlands 2Cardiology, John Radcliffe Hosp, Oxford, United Kingdom 3Cardiology, CardioVascular Cntr Frankfurt, Frankfurt Am Main, Germany 4Cardiology, Cardioangiologisches Centrum Bethanien, Frankfurt, Germany 5Unité de cardiologie interventionnelle, CHU Henri Mondor, Creteil, France 6Cardiology, Ospedale Ferrarotto, Catania, Italy 7Leiter Interventionelle Kardiologie, Cardiologicum Hamburg, Hamburg, Germany
Objective: Left Atrial Appendage Occlusion (LAAO) with Watchman has been found effective and non-inferior to oral anticoagulation (OAC) in randomized trials and prospective registries in pts with Atrial Fibrillation. The prospective, multi-center EWOLUTION registry aims to obtain real world clinical data on procedural success and complications, as well as long-term pt outcomes, including bleeding and incidence of stroke and TIA. Pts will be followed for 2 yrs according to the schedule and standard practice at the enrolling centers. Methods: 1025 pts scheduled for a WATCHMAN implant at 47 centers in 13 countries were prospectively enrolled over a time period of 19 months. Current ESC guidelines recommend LAA closure for pts with a (relative) contraindication for oral anticoagulation and increased risk of stroke. Here we report on periprocedural safety in this high-risk population. Results: Baseline data found the population to present with higher CHADS2 (2.8±1.3), CHADsVASc (4.5±1.6) and HAS-BLED (2.3±1.2) scores in comparison to previous RCT like PROTECT-AF and PREVAIL (CHADS2 2.2 ± 1.2 and 2.6 ± 1.0, respectively). 59.9% were male, mean age was 73.5±8.9, 34.3% had congestive heart failure, 55.9% were NYHA Class II and 31.3% were NYHA Class III. 15.6% had abnormal renal function. 10.6% had a history of TIA, 19.8% had a history of ischemic stroke and 14.8% had previous hemorrhagic stroke. 31.3% had a history of major bleeding. The investigators deemed 60.9% of the pts to be (relatively) contraindicated for oral anticoagulation. 99.3% of procedures were successful in closing the LAA with no/minimal (<5mm) leakage assessed by peri-procedural transesophageal echo. Despite the high-risk population, 93.1% of patients were free from any adverse event within the first 30 days of the implant procedure. Most notably, pericardial effusion occured only in 0.9% of the procedures. Device embolization was observed in only two cases (0.2%). Conclusion: LAA closure with the Watchman device has a high initial success rate in complete LAA closure with minimal periprocedural risk in appropriately trained hands even in multi-morbid patients. Improvements in implantation techniques and operator experience may further improve the net clinical benefit of the procedure.
Author Disclosures: L. Boersma: Honoraria; Modest; Boston Scientific. T. Betts: Honoraria; Modest; Boston Scientific. H. Sievert: Honoraria; Modest; Boston Scientific. B. Schmidt: Honoraria; Modest; Boston Scientific. E. Teiger: Honoraria; Modest; Boston Scientific. C. Tamburino: Honoraria; Modest; Boston Scientific. M. Bergmann: Honoraria; Modest; Boston Scientific.
Obesity and Cardiometabolic Health
Managing Risk Factors for CAD—Clinical Trial Updates
12126 Cholesterol Treatment Targets and Clinical Outcomes: A JUPITER Trial Update
Paul M Ridker, Samia Mora, Lynda Rose; on behalf of the JUPITER Trial Study Group; Medicine, Brigham & Womens Hosp, Boston, MA,
Background: Recent guidelines suggest that the benefits of statin therapy are relatively fixed and that on-treatment LDLC targets have a diminished role in patient management. Methods: In the randomized, double-blind, placebo-controlled JUPITER trial inclusive of 17,082 initially healthy men and women who were randomly allocated to rosuvastatin 20 mg or placebo and followed for up to 5 years, we (a) assessed the intra-individual variability in LDLC in response to statin therapy and (b) evaluated the impact of reaching 50 percent or greater reductions in LDLC on the risks of developing first ever myocardial infarction, stroke, or cardiovascular death. Results: While the median reduction in LDLC with rosuvastatin was 50%, individual variability was exceptionally wide, ranging from no reduction to reductions exceeding 85% (Figure, Left). Further, the magnitude of LDLC reduction directly related to the risks of first cardiovascular events during the follow-up period; at trial completion, incidence rates for the primary endpoint were 11.2, 9.2, 6.7, and 4.8 per 1000 person years for those in the placebo group and for those with no LDL reduction, LDL reductions <50 percent, and LDL reductions ≥50 percent, respectively. When compared to placebo, the hazard ratios for sequentially greater on-treatment percent reductions in LDLC were 0.91 (95%CI 0.54-1.53), 0.61 (95%CI 0.44-0.83), and 0.43 (95%CI 0.30-0.60) [p-trend across on-treatment LDL groups < 0.00001) (Figure, Right). Similar wide individual variability in statin response and similar relationships between percent reduction and clinical outcomes were observed in comparable analyses focusing on non-HDLC and apoB. Conclusion: The magnitude of lipid reduction following statin therapy varies widely for individual patients and on-treatment lipid levels are a major determinant of event reduction in primary prevention. These data have implications for practice and for the development of novel lipid lowering agents.
Author Disclosures: P.M. Ridker: Research Grant; Significant; Resaerch grants: AstraZeneca, Pfizer, Novartis. S. Mora: Research Grant; Significant; AstraZeneca. L. Rose: None.
14700 Relationship Between High-Density Lipoprotein Cholesterol and Cardiovascular and Non-Cardiovascular Mortality: A Population-Based Study of More than 630,000 Individuals Without Prior Cardiovascular Conditions in Ontario, Canada
Dennis T Ko1, David A Alter1, Helen Guo1, Maria Koh1, Geoffrey Lau2, Peter C Austin1, Gillian L Booth3, William Hogg4, Douglas S Lee1, Cynthia A Jackevicius1, Harindra C Wijeysundera1, John T Wilkins5, Jack V Tu1; 1Cardiology, Institute for Clinical Evaluative Sciences (ICES), Toronto, Canada 2Faculty of Health Science, McMaster, Hamilton, Canada 3Chronic Disease & Pharmacotherapy Rsch Program, Institute for Clinical Evaluative Sciences (ICES), Toronto, Canada 4Dept of Family Medicine, Univ of Ottawa, Ottawa, Canada 5Dept of Preventive Medicine, Northwestern Univ Feinberg Sch of Medicine, Chicago, IL,
Background: The prognostic importance of high-density lipoprotein cholesterol (HDL-C) as a modifiable risk factor of cardiovascular (CV) disease has been challenged. Our study was to explore the extent to which HDL-C levels are associated with non-cardiovascular risk factors and CV and non-CV mortality. Methods: Our cohort was created by linking together m large population-based databases. Residents aged 40 to 105 years in 2008, who had no prior cardiac conditions or severe comorbidities were eligible for inclusion. The primary outcome was cause-specific mortality (CV, cancer, and others). Cox proportional hazard models were constructed to estimate the hazard ratios of death associated with pre-specified HDL-C strata. Analyses were adjusted for age, income, non HDL-C levels, cardiac risk factors, and comorbidities, and stratified by sex. Results: Among the 631,762 individuals, their mean age was 57.2 years, 55.4% were women, and mean HDL-C level was 55.2 mg/dL. There were 17,952 deaths from any causes during a mean follow-up of 4.9 ± 0.4 years. Individuals with lower HDL-C levels were more likely to be at lower income, have unhealthy lifestyle, suboptimal cholesterol profile, more cardiac risk factors, and medical comorbidities. Low HDL-C levels were associated with higher hazards of CV, cancer, and other mortality (Figure). The dose-response associations between HDL-C levels and outcomes was non-linear, whereby patients whose HDL-C levels were very low and very high experienced a greater hazards of death than those whose HDL-C levels fell within intermediate HDL-C levels (41 - 80 mg/dL in men; 51 - 90 mg/dL in women). Conclusions: Individuals with low HDL-C levels were independently associated higher risk of CV and non-CV mortality. Complex associations between HDL-C levels and non-cardiac factors, and cause-specific mortality suggest it is a heavily confounded measure, which undermines the validity of making causal-inferences with cardiovascular disease.
Author Disclosures: D.T. Ko: None. D.A. Alter: None. H. Guo: None. M. Koh: None. G. Lau: None. P.C. Austin: None. G.L. Booth: None. W. Hogg: None. D.S. Lee: None. C.A. Jackevicius: None. H.C. Wijeysundera: None. J.T. Wilkins: None. J.V. Tu: None.
Key Words: HDL, Outcomes, Epidemiology
20210 Long-term Cardiovascular Effects of 4.9 Years of Intensive Blood Pressure Control in Type 2 Diabetes Mellitus: the Action to Control Cardiovascular Risk in Diabetes Follow-On Blood Pressure Study
William C Cushman1, Gregory W Evans2, Jeffrey A Cutler3, ACCORD/ACCORDION Study Group; 1Preventive Medicine Section (111Q), VA Med Cntr, Memphis, TN, 2Dept of Biostatistical Sciences, Wake Forest Sch of Medicine, Winston-Salem, NC, 3Consulting for Med Rsch, National Heart, Lung, and Blood Institute, Washington, DC,
Background: In the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD BP) trial a median of 4.9 years of intensive (systolic BP [SBP] <120 mm Hg) versus standard (SBP <140 mm Hg) BP lowering reduced stroke but not mortality or the primary cardiovascular (CV) outcome (nonfatal MI, nonfatal stroke, or CV death) in 4733 people with type 2 diabetes (T2DM) and high CV risk. Hypothesis: The ACCORD Follow-On (ACCORDION) study assessed the long-term effect of this intervention on the incidence of CV events or death. Methods: Cox regression analyses were conducted using an intention-to-treat approach for all randomized participants; those who died or declined further follow-up were censored at the most recent time for which data were available. Results: A total of 3957 (87% of participants alive at ACCORD’s end) were followed after the trial ended. ACCORDION participants were younger and healthier than non-participants. At trial close-out, mean SBP was 119 vs 134 mm Hg in the intensive and standard groups, respectively. The mean between group difference was 14.5 mm Hg. Two to five years after the end of trial, mean SBP was 130 vs 134 mm Hg in the intensive and standard groups, respectively, for an average difference of 4.2 mm Hg. During a median follow-up period of 8.8 years from randomization, the annual rate of the primary outcome (composite of nonfatal MI or stroke or CV death) was 2.03% in the intensive group and 2.22% in the standard group and hazard ratios (CI, p value) for incident outcomes in participants allocated to intensive versus standard BP lowering were 0.91 (0.79, 1.05, p=0.19) for the primary outcome; 1.04 (0.91, 1.19,p=0.59) for death; 0.87 (0.72, 1.06, p=0.16) for nonfatal MI; 0.85 (0.66, 1.10, p=0.22) for stroke; and 0.96 (0.75, 1.23, p=0.74) for CV death. Conclusions: In patients with T2DM at increased CV risk, 4.9 years of intensive BP lowering did not reduce the rate of a composite of fatal and non-fatal major CV events or mortality over a median follow-up of 8.8 years. The stroke benefit observed during the active intervention did not persist after BP differences waned.
Author Disclosures: W.C. Cushman: Research Grant; Modest; Merck, Eli Lilly. G.W. Evans: None. J.A. Cutler: None.
Key Words: Diabetes (Type II), Hypertension, Clinical trials
20266 Revascularization in Patients With Diabetes and Multivessel Coronary Artery Disease: A Population Based Evaluation of Outcomes
Krishnan Ramanathan1, Jim Abel2, Julie E Park3, Anthony Fung1, Min Gao3, Lillian Ding4, Carolyn M Taylor1, Karin H Humphries3, Michael E Farkouh5; 1Div of Cardiology, Univ of British Columbia, Vancouver, Canada 2Div of Cardiovascular Surgery, Univ of British Columbia, Vancouver, Canada 3Biostatistics and Epidemiology, BC Cntr for Improved Cardiovascular Health, Vancouver, Canada 4Biostatistics, Cardiac Services BC, Vancouver, Canada 5Div of Cardiology, Peter Munk Cardiac Cntr, Univ of Toronto, Toronto, Canada
In the setting of a randomized controlled trial (FREEDOM), stable diabetic patients with multivessel coronary artery disease (MV-CAD), revascularization with coronary artery bypass grafting (CABG) was a superior approach to percutaneous coronary intervention (PCI). We aimed to determine the applicability of these findings in a broad population with a high predominance of recent acute coronary syndrome (ACS) patients.
Provincial wide registries were linked to identify eligible patients and determine the primary endpoint. Diabetic patients with MV-CAD without restriction on kidney or heart function undergoing revascularization between 2007 and 2014 were eligible. The primary endpoint (MACE) was a composite of death, myocardial infarction (MI) and stroke, adjusted for differences in baseline risk factors.
There were n= 4937 procedures (PCI= 60%). PCI patients were older, more likely to be female, with higher rates of pulmonary and liver diseases (p<0.001). CABG patients had higher rates of proximal left anterior disease (p<0.001). The indication for revascularization was an ACS in 63%, but higher in PCI (68%) than CABG (54%) patients (p<0.001). The procedures were emergent or urgent in 59% of CABG and 70% of PCI patients (p<0.001). The CABG vs. PCI outcomes of MACE at 30-days [early] (A), MACE post 30 days to 12 months [short-term] (B) and components of MACE are shown in Figure 1. The benefit of CABG over PCI was significantly greater in ACS patients (pinteraction= 0.005) up to 30-days; while the benefit of CABG over PCI post 30-days did not differ between ACS vs. non-ACS patients (pinteraction= 0.791)
A real world, population-based evaluation corroborates the benefit of CABG over PCI in patients with diabetes and MV-CAD, both early and in the short-term. ACS patients experience an even greater benefit from CABG over PCI within the first 30 days. Our results require further evaluation and suggest a paradigm shift in the management of ACS patients with diabetes and MV-CAD.
Author Disclosures: K. Ramanathan: None. J. Abel: None. J.E. Park: None. A. Fung: None. M. Gao: None. L. Ding: None. C.M. Taylor: None. K.H. Humphries: None. M.E. Farkouh: None.
Key Words: Diabetes mellitus, Coronary artery bypass grafting (CABG), Percutaneous coronary intervention (PCI), Population science, Outcomes
2015 Late-Breaking Resuscitation Science Abstracts
Resuscitation Science Symposium
Late-Breaking Abstracts in Resuscitation Science
22949 Early Epinephrine for In-Hospital Cardiac Arrest Patients With a Shockable Rhythm
Lars W Andersen1, Tobias Kurth2, Katherine Berg3, Maureen Chase3, Michael Cocchi3, Michael Donnino3; 1Emergency Medicine, Aarhus Univ/Beth Israel Deaconess Med Cntr, Boston, MA, 2Univ of Bordeaux, Bordeaux, France 3Beth Israel Deaconess Med Cntr, Boston, MA,
Introduction: The AHA recommends administration of epinephrine after the 2nd shock in cardiac arrest patients with a shockable rhythm. Whether clinicians follow these guidelines and whether earlier epinephrine may be beneficial is unknown. Methods: This was an analysis of data from the Get With The Guidelines®-Resuscitation registry. We included adult in-hospital cardiac arrest patients with an initial shockable rhythm. We included patients who had a first defibrillation ≤ 2 min and remained in a shockable rhythm. We report the number of patients receiving epinephrine ≤ 2 min after the first shock. We compared survival between those receiving epinephrine ≤ 2 min after the first defibrillation with those not receiving epinephrine in this timeframe. We calculated a propensity score including multiple patient, event, and hospital characteristics and accounted for potential clustering within hospitals. Patients who received epinephrine at either 0, 1 or 2 min after the first defibrillation were propensity score-matched with a patient who were “at risk” of receiving epinephrine within the same minute (i.e., still undergoing resuscitation) but who did not receive epinephrine. We performed conditional logistic regression to assess the association between epinephrine administration and survival to hospital discharge and secondary outcomes. Results: 3673 patients were included. 1793 (49%) received epinephrine ≤ 2 min after the first defibrillation. 3536 patients were matched and the groups were well balanced (all p-values > 0.10 and standardized differences < 0.10). Epinephrine administration ≤ 2 min after the first defibrillation was associated with decreased odds of survival in the propensity score-matched analysis (OR: 0.64 [95%CI: 0.56 - 0.75], p < 0.001). Epinephrine administration was also associated with a decreased odds of ROSC (OR: 0.71 [95%: 0.62 - 0.83], p < 0.001) and good neurological outcome (OR: 0.69 [95%CI: 0.59 - 0.82], p < 0.001). Conclusion: In this cohort, half of patients with a persistent shockable rhythm received epinephrine ≤ 2 min after the first shock contrary to current AHA guidelines. The receipt of epinephrine ≤ 2 min after the first defibrillation was associated with decreased odds of ROSC, survival and good neurological outcome.
Author Disclosures: L.W. Andersen: None. T. Kurth: None. K. Berg: None. M. Chase: None. M. Cocchi: None. M. Donnino: Employment; Modest; American Heart Association.
Key Words: Cardiac arrest, Vasoconstrictor agents, Survival
23207 Early Oral Bisoprolol Reduces the Incidence, Duration and Mortality of Pulseless Ventricular Arrhythmias in Patients With Acute NSTEMI
Edd Maclean1, Sean Zheng2; 1Electrophysiology, Royal Brompton Hosp, London, United Kingdom 2King's College Hosp, London, United Kingdom
Background: Pulseless ventricular arrhythmias are a recognised complication of acute myocardial infarction. We investigated the impact of early oral beta blockade on the incidence and outcome of pulseless ventricular arrhythmias in patients with acute NSTEMI. Methods: We retrospectively identified 890 consecutive patients presenting with NSTEMI to a single UK centre between 2012-2014. All patients were given triple anti-thrombotic therapy at the point of diagnosis. Patients additionally received oral bisoprolol 1.25-2.5mg in the Emergency Department within 4 hours of presentation (‘Early group’), or on the admitting ward within 5-24 hours (‘Late group’). Medical records were analysed for the incidence, duration and outcome of pulseless ventricular tachycardia or fibrillation during inpatient stay. In the event of pulseless ventricular arrhythmia, patients were treated with adrenaline, amiodarone and defibrillation as per the UK Resuscitation Council Advanced Life Support guidelines. Results: In total 726 patients were included. Mean time to bisoprolol was 2.3±1.3 hours in the early group (n=189) versus 16.2±5.0 hours in the late group (n=537) [p=0.0001]. Patient characteristics were similar between the two groups. Prevalence of pulseless ventricular arrhythmias was significantly lower in the early group compared to the late group (3.2% vs 7.4% [p=0.038]). Mean time to return of spontaneous circulation (ROSC) was significantly shorter in the early group (5.4±4.4 minutes vs 15.2±10.1 minutes [p=0.021]). Failure of ROSC was significantly lower in the early group (16.7% vs 67.5% [p=0.028]). After adjusting for the confounders of pulse, blood pressure and smoking, logistic regression analysis identified early bisoprolol administration as protective for pulseless ventricular arrhythmia (p=0.031, OR 0.11, CI 0.02-0.81). Only 2 adverse beta blocker-related events were recorded. Conclusions: Early bisoprolol administration is safe and associated with reduced incidence, duration and mortality of pulseless ventricular arrhythmias in patients with acute NSTEMI.
Author Disclosures: E. Maclean: None. S. Zheng: None.
23167 Temporal Trends in Out-of-Hospital Cardiac Arrest in Southern Ontario
Jason E Buick1, Ian R Drennan2, Steven C Brooks3, Adam Byers2, Sheldon Cheskes4, Michael Feldman4, Minwook Lee2, Laurie J Morrison2, Damon C Scales5, Richard Verbeek4, Cathy Zhan2, Steve Lin6; 1Rescu, St Michael's Hosp, Toronto, Canada 2St Michael's Hosp, Toronto, Canada 3Queens Univ, Kingston, Canada 4Sunnybrook Cntr for Prehospital Medicine, Toronto, Canada 5Sunnybrook Health Sciences Cntr, Toronto, Canada 6Dept of Medicine, St Michael's Hosp, Toronto, Canada
Background: Considerable effort has gone into improving outcomes from out-of-hospital cardiac arrest, with studies showing increasing survival over time. These increases can be attributed to evidence based guidelines, higher rates of bystander CPR and improved prehospital CPR quality. In prior studies, measures of evidence based guidelines implementation are missing.
Objectives: To evaluate trends in OHCA survival over an 8-year period that included the implementation of the 2005 and 2010 AHA guidelines. Methods: This was a retrosepctive cohort study of all treated OHCA patients of presumed cardiac etiology between 2006 and 2014. Obvious etiology, EMS witnessed and pediatric (<18 years) arrests were excluded. Temporal changes were measured by chi-square trend analysis. Logistic regression evaluated associations between year of OHCA and survival. Results: A total of 25,568 patients were treated and met inclusion criteria. During the study period, survival nearly doubled (3.7% to 7.0%; p<0.01). Survival improved in patients with VF/VT (12.2% to 21.8%; p<0.01) and PEA (2.1% to 4.5%; p<0.01) but not asystole (p=0.78) as initial rhythms. Improvements were also seen in bystander CPR and AED use, EMS response time, chest compression fraction and depth, preshock pause, and incidence of PCI and targeted temperature management. When compared to 2006, survival was significantly better after 2010.
Conclusion: Survival after OHCA has improved over time, coinciding with the knowledge dissemination of the 2010 resuscitation guidelines. Additional work is required to evaluate how improving these measures could further improve survival and drive guideline implementation efforts.
Author Disclosures: J.E. Buick: None. I.R. Drennan: None. S.C. Brooks: Other; Modest; Travel reimbursement from the PulsePoint Foundation. A. Byers: None. S. Cheskes: None. M. Feldman: None. M. Lee: None. L.J. Morrison: None. D.C. Scales: None. R. Verbeek: None. C. Zhan: None. S. Lin: None.
Key Words: Sudden cardiac arrest, Emergency care, Emergency Medical Services
23165 Large Randomized Trial of Continuous versus Interrupted Chest Compressions in Out-of-hospital Cardiac Arrest: Results of the Resuscitation Outcomes Consortium CCC Trial
Graham Nichol1, Robter Schmicker2, Heny Wang3, Clifton Callaway4, Myron Weisfeldt5, George Sopko6, Laurie Morrison7, Sheldon Cheskes8, Jim Christenson9, Ron Straight10, Ahamed Idris11, S Marshal Isaacs12, Ian Stiell13, Christian Vaillancourt14, Peter Kudenchuk15, Thomas Rea15, Tom Aufderheide16, M Riccardo Colella16, Joseph Condle4, Shannon Stephens17, Joseph Richardson18, Brian Leroux15, Debra Egan19, Susanne May15, Joseph Ornato20; 1Prehospital Emergency Care, Univ of Washington - Harborview Cntr for Prehospital Emergency Care, Seattle, WA, 2Univ of Washington Clinical Trial Cntr, Seattle, WA, 3Univ of Alabama Sch of Medicine, Birmingham, AL, 4Univ of Pittsburgh, Pittsburgh, PA, 5Johns Hopkins Medicine, Baltimore, MD, 6NHLBI, NIH, Bethesda, MD, 7Rescu, Li Ka Shing Knowledge Inst., St. Michael's Hosp; Dept. of Medicine, UofT, Toronto, Canada 8Univ of Toronto, Toronto, Canada 9Univ of British Columbia, Vancouver, Canada 10Providence Health Care Rsch Institute, Vancouver, Canada 11Univ of Texas Southwestern Med Cntr, Dallas, TX, 12UTSW, Dallas, TX, 13Univ of Ottawa, Ottawa, Canada 14Ottawa Hosp Rsch Institute; Univ of Ottawa, Ottawa, Canada 15Univ of Washington, Seattle, WA, 16Med College of Wisconsin, Milwaukee, WI, 17Univ of Alabama at Birmingham, Birmingham, AL, 18Birmingham Fire and Rescue Service, Birmingham, AL, 19NHLBI, Bethesda, MD, 20Virginia Commonwealth Univ, Richmond, VA,
Importance: Manual chest compressions are interrupted frequently during treatment of out of hospital cardiac arrest (OHCA). These interruptions rapidly reduce blood flow. Objective: To assess if continuous manual chest compressions (CCC) versus manual chest compressions with interruptions for ventilations (ICC) affects survival, neurological status, or adverse events. Design: Randomized cluster design with crossover. Setting: 112 emergency medical services (EMS) agencies participating in the Resuscitation Outcomes Consortium (ROC) from June 6, 2011 to May 28, 2015. Participants: Adults with non-traumatic OHCA who received compressions from ROC EMS providers dispatched to the scene. Intervention: The intervention group received continuous compressions (CCC) with positive pressure ventilation without pauses. The control group received compressions with interruptions for ventilations at a ratio of 30 compressions to two ventilations (ICC). Main Outcome(s) and Measure(s): The primary outcome was survival to hospital discharge. Secondary outcomes included Modified Rankin scale (MRS, scored from 0 to 6, with ≤3 as favorable neurologic status). CPR process was measured to assess compliance with study treatment. Results: Of 23,698 patients included in the primary analysis, 12,647 were randomly assigned to the CCC group and 11,051 to the ICC group. As of June 14, 2015, vital status was available on 23,485 (99.1% of enrolled.) Results to date are provided (Table). Conclusions and Relevance: In this large cluster randomized effectiveness trial, continuous compressions with positive pressure ventilations as compared with compressions with interruptions for ventilations did not significantly improve overall survival or neurologic status. Trial Registration: ClinicalTrials.gov registration NCT01372748
Author Disclosures: G. Nichol: Employment; Significant; University of Washington via the Leonard A. Cobb Medic One Foundation Endowed Chair in Prehospital Emergency Care. Research Grant; Significant; National Heart Lung Blood Institute, Bethesda, MD. Resuscitation Outcomes Consortium (NIH U01 HL077863-05) 2004–2015; Co-PI, Food and Drug Administration, Silver Spring, MD, Cardiac Science Corp, Waukesha, WI, Heartsine Technologies Inc., Newtown, PA, Philips Healthcare Inc., Bothell, WA, Physio-Control Inc., Redmond, WA, ZOLL Inc., Chelmsford, MA, University of Washington Dynamic AED Registry, PI. 2013-2015. Other Research Support; Significant; Velomedix Inc., Menlo Park, CA. Velocity Pilot Study of Ultrafast Hypothermia in Patients with ST-Elevation Myocardial Infarction, Co-PI. 2014-2015. *Waived personal compensation.. Other; Modest; Travel: Abiomed Inc., Danvers, MA in 2015. R. Schmicker: Research Grant; Significant; 5U01 HL077863-University of Washington Data Coordinating Center. H. Wang: Research Grant; Significant; NHLBI, NINR. C. Callaway: Employment; Significant; UPMC Health System; University of Pittsburgh. Research Grant; Significant; NINDS; NHLBI. M. Weisfeldt: Research Grant; Significant; ROC. Ownership Interest; Significant; Board of Directors Vestin Corp. Consultant/Advisory Board; Significant; Vestin Corporation, FDA. G. Sopko: None. L. Morrison: None. S. Cheskes: Research Grant; Significant; NHLBI/CIHR Co PI Toronto ROC. Other Research Support; Significant; Speakers Honorarium Zoll Medical, Physio Control. J. Christenson: Research Grant; Significant; ROC. R. Straight: None. A. Idris: Research Grant; Significant; NIH/NHLBI. Consultant/Advisory Board; Significant; American Heart Association. S. Isaacs: None. I. Stiell: Research Grant; Significant; ROC. C. Vaillancourt: Research Grant; Significant; Ontario SPOR Support Unit (OSSU) IMPACT Award – Gov. of Ontario and CIHR, Ontario SPOR Support Unit (OSSU) IMPACT Award – Gov. of Ontario and CIHR, Natural Sciences and Engineering Research Council of Canada, Social Sciences and Humanities Research,, Social Sciences and Humanities Research, Canadian Association of Emergency Physicians, NIH, The Mach-Gaensslen Foundation of Canada, Heart and Stroke Foundation of Canada, Heart and Stroke Foundation of Ontario, Canadian Institutes of Health Research. P. Kudenchuk: Research Grant; Significant; NIH, ROC. Other Research Support; Significant; Heart Rescue. T. Rea: Research Grant; Modest; Medtronic Philanthropy, Philips Medical, Association of Public Safety Communication Officials. T. Aufderheide: Research Grant; Significant; NIH/NHLBI, NIH/NINDS, Department of Defense. M. Colella: Research Grant; Significant; NIH, ROC. J. Condle: Research Grant; Significant; ROC. S. Stephens: Research Grant; Significant; NIH, NHLBI, UT-Houston. J. Richardson: None. B. Leroux: Research Grant; Significant; NHLBI grant to UW Clinical Trials Center. D. Egan: None. S. May: Research Grant; Significant; NHLBI. Other; Modest; Non academic readers might not be aware that publications are essential for academic professional advancement and for receiving further funding. J. Ornato: Consultant/Advisory Board; Significant; Consultant and Cardiac Co-Chair, ROC.
Key Words: Cardiac arrest, Cardiopulmonary resuscitation, Resuscitation
Resuscitation Science Symposium
ReSS Poster Session - Day 3, Late Breaking Resuscitation Science
22952 Neighborhood Matters: Disparities in Process and Outcomes for Out-of-Hospital Cardiac Arrest in the Resuscitation Outcomes Consortium
Monique L Anderson1, Robert H Schmicker2, Eric D Peterson3, Jason Buick4, Ian R Drennan5, Heather Herren6, Jamie Jasti7, Peter Kudenchuk6, Michael Sayer6, Dion Stub8, Shannon W Stephens9, Graham Nichol6; 1Duke Clinical Rsch Institute, Duke Univ, Durham, NC, 2Univ of Washington, Seattle, NC, 3Duke Univ, Durham, NC, 4St. Michael's Hosp, Toronto, Canada 5St Michael's Hosp, Toronto, Canada 6Univ of Washington, Seattle, WA, 7Med College of Wisconsin, Milwaukee, WI, 8Alfred and Western Hosp, Baker IDI Heart and Diabetes Institute, Melbourne, Australia 9Univ of Alabama at Birmingham, Birmingham, AL,
Introduction: There are known racial differences in survival following out of hospital cardiac arrest (OHCA). It is unclear whether the quality of resuscitation care and outcomes vary as a function of the racial demographics of the neighborhood where the OHCA occurred. We used data from the Resuscitation Outcomes Consortium (ROC) to evaluate care process and outcomes of OHCA by % of black residents in the neighborhoods of the event. Methods: Patients were assigned to census tracts based on the location of arrest, then grouped within neighborhoods based on % black residents living in each census tract: <25%, 25-50%, 51-75%, or >75%. The primary outcome was survival to hospital discharge. Multi-level mixed effects logistic regression modeling examined the association between proportion of black residents and survival, adjusted for patient, neighborhood, and emergency medical services (EMS) characteristics. Results: Overall, 23,685 patients with OHCA at US ROC sites between 1/1/2008 and 12/31/2011 were included. Compared with neighborhoods with lower percentages of blacks, OHCA patients in neighborhoods with >75% blacks were less likely to be older, male, have an initial shockable rhythm, arrest in public location, or a bystander witnessed event. As the % black in neighborhood increased, the % receiving bystander CPR and lay AED use decreased (Table 1). EMS arrival times were shorter as % black in neighborhood increased, but % with return of spontaneous circulation was lower. After adjustment, OHCA in neighborhoods with a higher % of blacks had lower rates of survival to hospital discharge (>75% blacks: odds ratio (OR) 0.62 [95% CI: 0.47, 0.81]; 51-75% blacks: OR 0.65 [0.46,0.93]; 25-50% blacks: OR 0.76 [0.61,0.96]) compared with neighborhoods with <25% blacks. Conclusions: OHCA survival was significantly lower in neighborhoods with a higher percentage of black residents. Greater efforts are needed to improve resuscitation outcome in these neighborhood communities.
Author Disclosures: M.L. Anderson: None. R.H. Schmicker: None. E.D. Peterson: Research Grant; Significant; American College of Cardiology, Society of Thoracic Surgeons, American Heart Association. J. Buick: Other; Significant; evidence reviewer for a BLS worksheet for the 2015 ILCOR guidelines. I.R. Drennan: Employment; Significant; Rescu, Li Ka Shing Knowledge Insitute, St. Michael's Hospital, Institute of Medical Science, Faculty of Medicine, University of Toronto. H. Herren: None. J. Jasti: None. P. Kudenchuk: None. M. Sayer: None. D. Stub: Other Research Support; Significant; NHMRC/NHF Research fellowship. Nil Else. S.W. Stephens: None. G. Nichol: Employment; Significant; University of Washington via the Leonard A. Cobb Medic One Foundation Endowed Chair in Prehospital Emergency Care. Research Grant; Significant; National Heart Lung Blood Institute, Bethesda, MD. Resuscitation Outcomes Consortium (NIH U01 HL077863-05) 2004–2015; Co-PI, Food and Drug Administration, Silver Spring, MD; Cardiac Science Corp, Waukesha, WI; Heartsine Technologies Inc., Newtown, PA; Philips Healthcare Inc., Bothell, WA; Physio-Control Inc., Redmond, WA; Z. Other; Modest; Velomedix Inc., Menlo Park, CA. Velocity Pilot Study of Ultrafast Hypothermia in Patients with ST-Elevation Myocardial Infarction, Co-PI. 2014-2015. *Waived personal compensation.
Key Words: cardiac resuscitation, cardiopulmonary resuscitation, health disparities
23188 Atrial Fibrillation Accompanies a Switch From the Dominant α-mhc to the β-mhc Isoform
Salah A. Mohamed1, Thorsten Hanke2, Oliver Klein3, Junfeng Yan2, Sebastian Sommer4, Stefani Sommer4, Herbert Thiele5; 1Dept of Cardio and Thoracic Vascular Surgery, Univ of Luebeck, Luebeck, Germany 2Univ of Luebeck, Luebeck, Germany 3Charité-Med Univ, Berlin, Germany 4Univ Clinic Wuerzburg, Wuerzburg, Germany 5Fraunhofer MEVIS, Luebeck, Germany
Introduction: Atrial fibrillation (AF) poses a challenge to our growing elderly population; a significant proportion of AF patients are misclassified by clinical categorization. We performed a proteomic analysis of the left atrial appendage tissue obtained from patients with normal sinus rhythm (SR) compared with samples of patients suffering from AF subtypes (paroxysmal, persistent, and long-standing persistent). Methods: MALDI imaging mass spectrometry (MALDI-IMS) was used to differentiate and classify the appendage tissue resected routinely during the MAZE procedure via direct (in situ) analysis of formalin-fixed paraffin embedded (FFPE) tissue samples. Furthermore, relative gene expression profiles for Myh6, Myh7, and microRNA-208a were generated using quantitative real-time Polymerase Chain Reaction. Results: Using receiver operating characteristic analysis (AUC > 0.7) characteristic intensity distribution of given m/z values, which are discriminative for the considered cluster, was determined to distinguish between paroxysmal vs persistent AF, and persistent vs long-persistent AF (persistent vs. long-standing persistent, 1.59 ± 0.12 vs. 6.85 ± 3.02, p = 0.02). A highly significant increase in the Myh7 expression in AF compared with that in the SR tissue samples was detected (63.1 ± 12.6 vs. 11.4 ± 1.9, p = 0.001). A significant difference in the MYH6/MYH7 ratio between SR and each of the AF subtypes was detected. Considering paroxysmal, persistent, and long-standing persistent AF, the p-values of the differences were 0.007, 0.019, and 0.010, respectively. The difference in the microRNA 208a expression level between persistent and long-standing persistent AF proved to be significant (3.3 ± 0.8 vs. 1.0 ± 0.2, p = 0.02). Conclusions: The tissue-based proteomic approach provides clinically relevant information that will be beneficial in improving the risk stratification in AF patients. The coding of an intron in the Myh6 gene by microRNA-208a is a likely deciding factor in the regulation of β-MHC expression.
Author Disclosures: S. Mohamed: None. T. Hanke: None. O. Klein: None. J. Yan: None. S. Sommer: None. S. Sommer: None. H. Thiele: None.
Key Words: Atrial Fibrillation
23288 Natural History of Automated External Defibrillators in Public Locations
Graham Nichol1, Siobhan Brown2, Lance Becker3, Raina Merchant3, Ben Abella3, Benjamin Eloff4, Scott Youngquist5, David Salcido6, Sara Tisherman6, Terry Valenzuela7, Mohamud Daya8, Jo Ann Elrod2, Deborah Fly2, Susanne May9, Michael Sayre2, Michael Sayre2; 1General Internal Medicine, Univ of Washington - Harborview Cntr for Prehospital Emergency Care, Seattle, WA, 2Univ of Washington - Harborview Cntr for Prehospital Emergency Care, Seattle, WA, 3Univ of Pennsylvaia, Philadelphia, PA, 4Food and Drug Administration, Silver Spring, MD, 5Univ of Utah, Salt Lake City, UT, 6Univ of Pittsburgh, Pittsburgh, PA, 7Univ of Arizona, Tucson, AZ, 8Oregon Health Sciences Univ, Portland, OR, 9Univ of Washington, Seattle, WA,
Introduction: Use of an AED by a layperson before the arrival of emergency medical services (EMS) providers on the scene is the only field intervention known to improve survival after cardiac arrest. AEDs are placed in public locations and private businesses to be available for use by laypersons when cardiac arrest is observed. There are challenges to use and maintenance of AEDs. They may be moved from one location to another. They differ in size and other features. They require periodic confirmation of availability for use, replacement of batteries or leads, as well as software updates. Accurate knowledge of AED location and availability for use is essential for EMS dispatchers to be able to guide laypersons in how to access and use them before arrival of EMS providers on scene. This study used data from the Dynamic AED Registry to describe the natural history of location and non-clinical use of AEDs in public locations. Methods: AEDs were identified by supplementing preexisting public and private registries with crowdsourcing methods. Each AED is tagged with a 2D matrix code label to serve as a dynamic unique device identifier. AEDs are tracked by rescanning labels with every non-clinical and clinical use. Reasons for non-clinical use were summarized descriptively. Time to non-clinical event was evaluated using Kaplan-Meier methods. Results: As of 13 August 2015, 2,189 unique devices had been tagged for between 0 and 510 days (median 162, Q1-Q3: 83-358). Non-clinical reasons to rescan were: confirmation of readiness for use (86%); battery and leads change (6%); other maintenance (2%); other (2%); battery change (1%); device lead change (1%), multiple simultaneous reasons (2%), and taking AED out of service (1%). Conclusions: The status of AEDs in public locations changes over time. Tracking AED location and use over time is feasible. Periodic reassessment of AED status is necessary to improve the community response to out of hospital cardiac arrest by laypersons.
Author Disclosures: G. Nichol: Employment; Significant; University of Washington via the Leonard A. Cobb Medic One Foundation Endowed Chair in Prehospital Emergency Care. Research Grant; Significant; Food and Drug Administration, Silver Spring, MD, Cardiac Science Corp, Waukesha, WI, Heartsine Technologies Inc., Newtown, PA, Philips Healthcare Inc., Bothell, WA, Physio-Control Inc., Redmond, WA, Zoll Inc., Chelmsford, MA, University of Washington Dynamic AED Registry, PI 2013-2015, National Heart Lung Blood Institute, Bethesda, MD, Resuscitation Outcomes Consortium (NIH U01 HL077863-05) 2004-2015; Co-PI, National Heart Lung Blood Institute, Bethesda, MD. Pragmatic Trial of Airway Management in Out-of Hospital Cardiac Arrest, NIH UH3HL125163-02 2013-2016; Co-I. S. Brown: None. L. Becker: None. R. Merchant: None. B. Abella: None. B. Eloff: None. S. Youngquist: None. D. Salcido: None. S. Tisherman: None. T. Valenzuela: None. M. Daya: None. J. Elrod: None. D. Fly: None. S. May: None. M. Sayre: None. M. Sayre: None.
Key Words: Cardiac Arrest, AEDs, Public Health
22895 The Norwegian Cardio-Respiratory Arrest Study - NORCAST
Espen R Nakstad1, Henrik Staer-Jensen2, Geir O Andersen2, Christofer Lundqvist3, Dag Jacobsen2, Jan Eritsland2, Kjetil Sunde2; 1Dept of Acute Medicine, Oslo Univ Hosp, Oslo, Norway 2Oslo Univ Hosp, Oslo, Norway 3Akershus Univ Hosp, Lorenskog, Norway
Background: Early prediction of outcome in resuscitated out-of-hospital cardiac arrest (OHCA) patients carries huge ethical implications and remain a difficult task for physicians. In this clinical prospective study, we followed admitted comatose OHCA patients to asses if combinations of prognostic markers can predict good or poor neurological outcome (Cerebral Performance Category (CPC) 1-2 or 3-5, respectively) with specificity and sensitivity levels high enough for practical clinical use. In order to avoid misinterpretation, premature withdrawal of intensive care or self-fulfilling prophecies not based on evidence, study examinations were blinded to the clinicians. Methods: All comatose patients > 18 years of age were included on arrival to Oslo University Hospital. Biomarkers (Serum NSE, S-100B and Pro-Calcitonin) were sampled 24h, 48h, 72h, 5 and 7 days after OHCA. EEG, SSEP (Somato-Sensory Evoked Potential) and Transcranial Doppler registrations were performed during therapeutic hypothermia (33-34 Celsius) and minimum 72 hours after normothermia and withdrawal of sedatives. A standardized neurological examination was performed in addition to daily GCS and brain stem reflex scores. Cerebral MRi was performed 5-7 days post arrest in as many patients as practically possible. Primary: endpoint was CPC 1-2 six months post arrest, based on clinical and cognitive function tests. An expert study committee retrospectively reviewed all patient records in detail and divided patients into groups based on the causes of arrest; 1) Acute Myocardial Infarction, 2) Chronic Coronary Disease, 3) Arrhythmic Cardiac Arrest, 4) Hypoxic Cardiac Arrest, 5) Respiratory Arrest/ Severe hypoxia, 6) Other Non-traumatic Cause of Coma, and 7) Unknown. In addition, the cause of death was considered in all non-survivors and divided into the following categories; 1) Certain cerebral cause of death, 2) Most likely cerebral death, 3) Certain cardiac cause, 4) Most likely cardiac cause, and 5) Other/uncertain. Summary/Results: Six months after cardiorespiratory arrest, more than 50% of the patients were alive with a good neurological outcome. Among these, more than 80% scored CPC 1. Prognostic markers are currently being analyzed and will be subject to statistical analysis.
Author Disclosures: E.R. Nakstad: None. H. Staer-Jensen: None. G.O. Andersen: None. C. Lundqvist: None. D. Jacobsen: None. J. Eritsland: None. K. Sunde: None.
Key Words: Advanced life support, Resuscitation, Sudden death
22984 Public Cardiac Arrest Characteristics in Enclosed Pedestrian Networks
Minha Lee1, Derya Demirtaş2, Jason E Buick2, Amy Ng2, Michael J Feldman2, Sheldon Cheskes2, Laurie J Morrison2, Timothy C Chan2; 1Dept of Mechanical and Industrial Engineering, Univ of Toronto, Toronto, Canada 2Univ of Toronto, Toronto, Canada
Background: Cities around the world have underground or above-ground enclosed networks for pedestrian travel, representing unique environments for studying out-of-hospital cardiac arrest (OHCA) and resuscitation. The characteristics of OHCAs that occur in such networks are unknown. Objective: To determine whether cardiac arrests occurring in enclosed pedestrian networks are different from those in the encompassing city, using the PATH network in Toronto, the largest underground shopping complex in the world, as a model site. Methods: We identified all atraumatic, public-location OHCAs in Toronto from Apr. 2006 – Mar. 2015, and classified them according to location: Toronto, downtown, and PATH-accessible. PATH-accessible OHCAs are those that occur within the PATH network between the first underground and second above-ground floor. We collected demographic, prehospital intervention, and survival data for each OHCA. Statistical analysis was performed using t-tests and chi-squared tests. Results: We identified 2621 atraumatic public OHCAs, of which 521 were in downtown and 50 were PATH-accessible. Compared to Toronto overall, PATH-accessible OHCAs had significantly higher proportions of bystander witnessed interventions, initial shockable rhythm, and overall survival, with all differences being statistically significant. Similar significant differences were observed when comparing PATH-accessible to downtown OHCAs. There were no significant differences in demographics and survival among patients with initial shockable rhythm. Conclusion: This study suggests that OHCAs in enclosed pedestrian networks are uniquely different from other public settings. Bystander resuscitation efforts are significantly more frequent and survival rates are higher. Urban planners in similar networks worldwide should consider these findings when deciding on AED placement and how to cue bystander response.
Author Disclosures: M. Lee: None. D. Demirtaş: None. J.E. Buick: None. A. Ng: None. M.J. Feldman: None. S. Cheskes: Honoraria; Modest; Received for speaking on CPR quality for Zoll Medical and Physio Control. L.J. Morrison: None. T.C. Chan: None.
Key Words: Resuscitation, Cardiac arrest, Survival
- © 2015 American Heart Association, Inc.