2013 Late-Breaking Clinical Trial Abstracts
- Late-Breaking Clinical Trials: Acute Cardiovascular and Cerebrovascular Care
- Late-Breaking Clinical Trials: Prevention: From Schools to Countries
- Late-Breaking Clinical Trials: Medical and Surgical Approaches to Improving Heart Failure Outcomes
- Late-Breaking Clinical Trials: Therapeutic Advances in Coronary and Peripheral Vascular Disease
- Late-Breaking Clinical Trials: New Strategies for Atrial Fibrillation Patients: Rhythm and Thrombosis
- Clinical Science: Special Reports: Application of Cell-Based Therapies to Treat Cardiac and Peripheral Diseases
- Clinical Science: Special Reports: Biomarkers in Populations
- Clinical Science: Special Reports: Novel Approaches to Treating Hypertension and Atherosclerosis
- Clinical Science: Special Reports: Advanced Cardiovascular Disease: Complications and Challenges
- Session XIV: Late-Breaking Abstracts in Resuscitation Science
- Session VIII: Best Original Resuscitation Science Poster Session and Reception
- Figures & Tables
- Info & Metrics
Late-Breaking Clinical Trials: Acute Cardiovascular and Cerebrovascular Care
Nitrites in Acute Myocardial Infarction
Nishat Siddiqi1, Margaret Bruce1, Christopher J. Neil1, Graeme MacLennan2, Seonaidh Cotton2, Sofia A. Papadopoulou3, Baljit Jagpal1, Sue Brown3, Fatima Perez Gonzalez3, Satnam Singh1, Konstantin Schwarz1, Martin Feelisch4, Nicholas Bunce5, Pitt O Lim5, David Hildick-Smith6, John Horowitz7, Melanie Madhani8, Nicholas Boon9, Dana Dawson10, Juan-Carlos Kaski3, Michael P Frenneaux10. 1Dept of Cardiovascular Rsch, Univ of Aberdeen, Aberdeen, United Kingdom, 2Health Sciences Building (third floor), Centre for Healthcare Randomised Trials (CHaRT), Aberdeen, United Kingdom, 3Cardiovascular Sciences Rsch Centre, St George’s Univ of London, London, United Kingdom, 4Faculty of Medicine, Univ of Southampton, Southampton, 5Cardiology Dept, St George’s Healthcare NHS Trust, 6Cardiology Research Unit, Brighton and Sussex Univ Hospitals, Brighton, United Kingdom, 7Basil Hetzel Unit for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, 8Centre for Cardiovascular Sciences, Univ of Birmingham, Birmingham, United Kingdom, 9Centre for Cardiovascular Sciences, Univ of Edinburgh, Edinburgh, United Kingdom, 10School of Medicine and Dentistry, Univ of Aberdeen, Aberdeen
Introduction:Despite reperfusion therapy for acute myocardial infarction (AMI), heart failure remains a major sequel. Reperfusion leads to further damage, described as ischemia-reperfusion-injury (IRI). This contributes up to 50% of the final infarct size. In pre-clinical models nitrite potently protects against IRI in the heart and other organs. Hypothesis:Intravenous (iv) sodium nitrite, administered immediately before opening of the infarct-related artery, results in significant reduction of IRI in patients with acute ST elevation MI (STEMI). Methods:In this phase II, randomised, placebo-controlled, double-blind, multicentre trial, 220 patients with first acute STEMI and TIMI 0 or 1 flow were randomised in a double-blind fashion to 70micromol iv sodium nitrite or matching placebo over 5 minutes immediately preceding opening of the infarct-related artery. The primary end point was the difference in infarct size between sodium nitrite and placebo groups using cardiovascular magnetic resonance imaging (CMR) at 6-8 days following AMI, adjusted for area at risk (AAR), diabetes status and center. Secondary end points comprised (i) Infarct size (CMR) at six months; (ii) plasma CK and Troponin I measured over 72 hours after injection of the study medication; (iii) Infarct size corrected for AAR measured using T2 weighted CMR; (iv) left ventricular (LV) ejection fraction and LV end systolic volume index measured by CMR at 6-8 days and at six months. Results: Infarct size at 6-8 days by CMR did not differ between nitrite and placebo groups (effect size -0.7% 95%CI -2.2,+0.7; p=0.34). There were no significant differences in the predefined secondary end points. There was no treatment effect in non-diabetics, but in diabetics was -4.5% (95%CI -8.8,-0.2; p=0.041) but the interaction was not significant (p=0.067). Conclusion: Sodium nitrite administered iv immediately prior to reperfusion in patients with acute STEMI did not reduce infarct size. A potential benefit in diabetics warrants further study. Funding, Ethics, Regulatory Approvals and Registration: This study was funded by the UK Medical Research Council. All UK regulatory approvals were obtained. NCT01388504 and ISRCTN57596739.
Author Disclosures: N. Siddiqi: None. M. Bruce: None. C.J. Neil: None. G. MacLennan: None. S. Cotton: None. S.A. Papadopoulou: None. B. Jagpal: None. S. Brown: None. F. Perez Gonzalez: None. S. Singh: None. K. Schwarz: None. M Feelisch: None. N. Bunce: None. P.O. Lim: None. D. Hildick-Smith: None. J. Horowitz: None. M. Madhani: None. N. Boon: None. J. Kaski: None. D. Dawson: None. M.P. Frenneaux: None.
Key Words: Myocardial infarction, STEMI; Percutaneous coronary intervention; Reperfusion injury; Cardioprotection; Cardiac MRI
Blood Pressure Reduction Among Acute Ischemic Stroke Patients: A Randomized Controlled Clinical Trial
Jiang He1, Yonghong Zhang2, Tan Xu2, Weijun Tong2, Shaoyan Zhang2, Chung-Shiuan Chen1, Qi Zhao1, Jing Chen1; 1Dept of Epidemiology, Tulane Univ, New Orleans, LA, 2Dept of Epidemiology, Soochow Univ, Suzhou, China
Stroke is a major cause of death and disability globally. We conducted a randomized controlled trial to test the effect of blood pressure (BP) reduction on short-term case-fatality and major disability among patients with acute ischemic stroke in China. From August 2009 to May 2013, we recruited 4,071 patients with acute (within 48 hours of onset) ischemic stroke, with a systolic BP ≥140 mmHg. They were randomly assigned to antihypertensive treatment (lowering systolic BP by 10-25% within the first 24 hours after randomization and BP <140/90 mmHg within 7 days) or control (discontinuing all home antihypertensive medications). The primary outcome was a combination of death and major disability (defined by a modified Rankin scale ≥3) at 14 days or discharge and at 3 months. The secondary outcome was recurrent stroke, death, and vascular events during 3-months of follow-up. Mean systolic blood pressure was reduced from 166.7 mmHg to 144.7 (-12.7%) within 24 hours and to 135.2 by day 14 in the treatment group and from 165.6 mmHg to 152.9 (-7.2%) within 24 hours and to 143.7 by day 14 in the control group (p<0.0001 for group-differences). The primary outcome event rate was 33.6% in the treatment group and 33.6% in the control group (p=0.98) at 14 days or discharge. The primary outcome event rate was 25.2% in the treatment group and 25.3% in the control group (p=0.93) at 3 months. The event rates of recurrent stroke, vascular disease, and all-cause mortality were 1.4% and 2.2% (p=0.07), 2.4% and 3.0% (p=0.28), and 3.4% and 2.7% (p=0.20) in the treatment and control groups, respectively. In conclusion, this randomized trial indicates that antihypertensive treatment in patients with acute ischemic stroke within 48 hours of symptom onset does not reduce or increase death and major disability.
Author Disclosures: J. He: None. Y. Zhang: None. T. Xu: None. W. Tong: None. S. Zhang: None. C. Chen: None. Q. Zhao: None. J. Chen: None.
Key Words: Blood pressure; Antihypertensive agents; Stroke
Randomized Clinical Trial of Pre-hospital Induction of Mild Hypothermia in Out-of-Hospital Cardiac Arrest Patients Using a Rapid Infusion of 4oC Normal Saline
Francis Kim1, Graham Nichol2, Charles Maynard3, Al Hallstrom2, Peter Kudenchuk1, Thomas Rea2, Michael Copass4, David Carlbom2, Steven Deem5, WT Longstreth4, Michele Olsufka2, Leonard Cobb1; 1Medicine/Cardiology, Univ of Washington, Seattle, WA, 2Medicine, Univ of Washington, Seattle, WA, 3Health Services, Univ of Washington, Seattle, WA, 4Neurology, Univ of Washington, Seattle, WA, 5Anesthesiology, Univ of Washington, Seattle, WA
Background: In animal models of cardiac arrest, the benefit of therapeutic hypothermia declines when initiated more than 15 minutes after reperfusion. Although delayed hospital cooling has been demonstrated to improve outcome after cardiac arrest, pre-hospital cooling started immediately following return of spontaneous circulation may be more beneficial. The aims of this randomized clinical trial were to determine whether early in-field cooling improves survival and functional status in resuscitated cardiac arrest patients with ventricular fibrillation (VF) and without (non-VF). Methods: In a prospective, randomized clinical trial, we assigned adults with out-of-hospital cardiac arrest to either rapid pre-hospital cooling with an infusion of up to 2 liters of 4oC normal saline as soon as possible following resuscitation or to standard care. Nearly all of the resuscitated VF patients admitted to the hospital received hospital cooling regardless of their randomization. The primary outcome was survival to hospital discharge and functional status at discharge. Results: A total of 1359 patients (583 VF and 776 non-VF) were randomized to receive standard care with or without pre-hospital cooling. Among patients with VF, the intervention group had a mean core temperature decrease of 1.2 C +1.1 by hospital arrival, achieving a temperature of less than 34 C 1.3 hours sooner than the standard care group. Survival to hospital discharge was 62.5% in the intervention group vs. 64.3% in the control group, p=0.69. Among patients with non-VF, survival to discharge was 19.2% in the intervention group vs. 16.3% in the control group, p=0.3. Regardless of the initial rhythm, functional status at discharge was not significantly different between the treatment and control groups. The intervention was associated with increased incidence of re-arrest in the field (26% vs. 21%, p=0.007) as well as pulmonary edema on first chest x-ray and increased diuretic use, which all resolved within 12 hours after admission. Conclusions: Although use of early, pre-hospital cooling reduced core temperature by hospital arrival and reduced the time to reach 34 C, it did not improve survival or functional status among patients resuscitated from out-of-hospital VF or non-VF.
Author Disclosures: F. Kim: None. G. Nichol: None. C. Maynard: None. A. Hallstrom: None. P. Kudenchuk: None. T. Rea: None. M. Copass: None. D. Carlbom: None. S. Deem: None. W. Longstreth: None. M. Olsufka: None. L. Cobb: None.
Key Words: Cardiac arrest; Hypothermia; Ventricular fibrillation
Target Temperature Management 33°C versus 36°C after Out-of-hospital Cardiac Arrest, a Randomized, Parallel Group, Assessor Blinded Clinical Trial
Niklas Nielsen1, Jørn Wetterslev2, Tobias Cronberg3, David Erlinge4, Yvan Gasche5, Christian Hassager6, Janneke Horn7, Jan Hovdenes8, Jesper Kjaergaard6, Michael Kuiper9, Tommaso Pellis10, Pascal Stammet11, Micahel Wanscher6, Matthew P Wise12, Anders Åneman13, Nawaf al-Subaie14, Søren Boesgaard6, Jon Bro-Jeppesen6, Iole Brunetti15, Jan F Bugge16, Christopher D Hingston12, Nicole Juffermans7, Matty Koopmans17, Lars Køber6, Jørund Langørgen18, Gisela Lilja3, Jakob E Møller6, Malin Rundgren19, Christian Rylander20, Ondrej Smid21, Christophe Werer22, Per Winkel2, Hans Friberg19; 1Dept of Anesthesiology and Intensive Care, Helsingborg Hosp, Lund Univ, Helsingborg, Sweden; 2Copenhagen Trial Unit, Copenhagen Univ Hosp, Copenhagen, Denmark; 3Dept of Neurology, Lund Univ Hosp, Lund, Sweden; 4Dept of Cardiology, Lund Univ Hosp, Lund, Sweden; 5Dept of Intensive Care, Geneve Univ Hosp, Geneve, Switzerland; 6Heart Cntr, Copenhagen Univ Hosp, Copenhagen, Denmark; 7Dept of Intensive Care, Academic Med Cntr, Amsterdam, Netherlands; 8Anesthesiology and Intensive Care, Oslo Univ Hosp, Oslo, Norway; 9Dept of Intensive Care, Leeuwarden Med Cntr, Leeuwarden, Netherlands; 10Dept of Intensive Care, Santa Maria degli Angeli Hosp, Pordenone, Italy; 11Dept of Intensive Care, Cntr Hospier de Luxembourg, Luxembourg, Luxembourg; 12Dept of Adult Critical Care, Univ Hosp of Wales, Cardiff, United Kingdom; 13Dept of Intensive Care, Liverpool Hosp, Liverpool, Sydney, Australia; 14Dept of Intensive Care, St George Hosp NHS Trust, Tooting, London, United Kingdom; 15Dept of Intensive Care, San Martino Hosp, Genoa, Italy; 16Dept of Anesthesiology and Intensive Care, Oslo Univ Hosp, Oslo, Norway; 17Dept of Intensive Care, Leeuwarden Med Cntr, leeuwarden, Netherlands; 18Dept of Cardiology, medical intensive care unit, Haukeland Univ Hosp, Bergen, Norway; 19Dept of Anesthesiology and Intensive Care, Lund Univ Hosp, Lund, Sweden; 20Dept of Anesthesiology and Intensive Care, Sahlgrenska Univ Hosp, Göteborg, Sweden; 21Critical Care Unit, General Univ Hosp in Prague, Prague, Czech Republic; 22Dept of Anesthesiology and Intensive Care, Cntr Hospier de Luxembourg, Luxembourg, Luxembourg
Introduction and objective: Unconscious patients with return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) have a high risk of death and poor neurological function. Temperature regulation is recommended in guidelines to improve outcome, but the optimal target temperature management strategy is not known. Our objective was to test two essentially different temperature levels, both avoiding hyperthermia, on the outcomes of survival and poor neurological function. Methods: In a multi-center, parallel-group, assessor blinded trial, conducted in 36 intensive care units, we centrally randomized 950 unconscious adults with ROSC after OHCA of presumed cardiac cause, to a target temperature management of 33°C or 36°C. The primary outcome is survival until end of trial (180 days after last randomization) adjusted for site as the stratification variable. The secondary outcomes are poor neurological function or death at 180 days and adverse events (bleeding, infection, arrhythmia, electrolyte- and metabolic disturbances) within the first seven days. Secondary multi-variate analyses will be performed adjusting for age, gender, initial rhythm, time to ROSC and presence of shock at admission. Results: Nine hundred and fifty patients were randomized between November 2010 and January 2013. The cohort baseline characteristics are: median age 65 years (inter quartile range 56-73), 81 % male gender, and 78 % ventricular fibrillation or non-perfusing tachycardia. The last follow up will be performed in July 2013. Data on demographics, temperature and critical care management, primary outcome (survival) and secondary outcomes (neurological function and adverse events) will be presented. Conclusion: The target temperature management 33°C versus 36°C after out-of-hospital cardiac arrest-trial is the largest trial to date investigating target temperature management after cardiac arrest. Results will be available end of August. (NCT01020916)
Author Disclosures: N. Nielsen: None. J. Wetterslev: None. T. Cronberg: None. D. Erlinge: None. Y. Gasche: None. C. Hassager: None. J. Horn: None. J. Hovdenes: None. J. Kjaergaard: None. M. Kuiper: None. T. Pellis: None. P. Stammet: None. M. Wanscher: None. M.P. Wise: None. A. Åneman: None. N. al-Subaie: None. S. Boesgaard: None. J. Bro-Jeppesen: None. I. Brunetti: None. J.F. Bugge: None. C.D. Hingston: None. N. Juffermans: None. M. Koopmans: None. L. Køber: None. J. Langørgen: None. G. Lilja: None. J.E. Møller: None. M. Rundgren: None. C. Rylander: None. O. Smid: None. C. Werer: None. P. Winkel: None. H. Friberg: None.
Key Words: Cardiac arrest; Hypothermia; Outcomes
Late-Breaking Clinical Trials: Prevention: From Schools to Countries
Promotion of Cardiovascular Health in Preschool Children: 36-month Cohort Follow-up
Jaime Céspedes1, German Briceño1, Michael Farkouh2, Rajesh Vedanthan3, Jorge Baxter4, Martha Leal1, Paolo Boffetta3, Marilyn Hunn3, Rodolfo Dennis5, Valentin Fuster6; 1Pediatría, Fundación CardioInfantil Instituto de Cardiología, Bogotá, Colombia; 2Cardiology, Icahn Sch of Medicine at Mount Sinai; Peter Munk Cardiac Cntr and Li Ka Shing Knowledge Institute, Univ of Toronto, Toronto, Canada; 3Cardiology, Icahn Sch of Medicine at Mount Sinai, New York, NY, 4Global Education, Sesame Workshop, New York, NY, 5Investigaciones, Fundación CardioInfantil Instituto de Cardiología, Bogotá, Colombia; 6Cardiology, Icahn Sch of Medicine at Mount Sinai; Cntr Nacional de Investigaciones Cardiovasculares, New York, NY
Background: Educational interventions in preschool children could improve dietary behavior and physical activity, and prevent unhealthy body weights in low- and middle- income countries. We have previously reported the beneficial impact of an educational intervention in preschoolers in a six month trial. We now report extended results after 36 months. Methods: Evaluating the cohort of previously intervened children, baseline measurements were made in May 2009 in 14 preschool facilities in Usaquén (Bogotá, Colombia). Follow-up measurements were performed at 18 and 36 months. The primary outcome was the mean change in children's knowledge and attitudes scores regarding healthy eating and living an active lifestyle, including habits scores related to physical activity. Secondary outcomes were the change over time of children's nutritional status and the mean change in parent's knowledge, attitudes and habits. RESULTS: We included 1,216 children, 3-5 years of age, and 928 parents. After adjusting by sex and age of children, socioeconomic status, age of parents, age and education level of teachers, we found a significant increase in mean knowledge, attitudes and habits scores at 36 months, compared to baseline: 87.94 vs. 76.15 (p<0.001); 86.39 vs. 57.03 (p<0.001); and 66.29 vs. 48.72 (p<0.001) respectively. We observed a similar increase in knowledge and attitude scores in parents:73.45 vs. 70.01 (p<0.001); and 78.08 vs. 74.65(p<0.001). The proportion of eutrophic children increased from 62.1% at baseline to 75.0% at 36 months (p<0.0001). Conclusions: After 36 months, the educational intervention maintained a beneficial trend towards a healthy lifestyle in children and their parents. Key Words: Cardiovascular disease prevention • Nutrition • Physical activity
Author Disclosures: J. Céspedes: None. G. Briceño: None. M. Farkouh: None. R. Vedanthan: None. J. Baxter: None. M. Leal: None. P. Boffetta: None. M. Hunn: None. R. Dennis: None. V. Fuster: None.
Key Words: Health promotion; Health education; Cardiovascular disease prevention; Behavior change; Community-based care
Randomized Trial of Social Network Lifestyle Intervention for Obesity: MICROCLINIC Intervention Results and 16-Month Follow-up
Eric L Ding1, Kathleen T Watson2, Nancy Bui2, Leila Makarechi2, Leslie Lang2, Marta R Prescott2, Sha'Tia N Safford3, Dipti Banerjee3, Harold W Campbell4, Josh A Rushakoff4, Daniel E Zoughbie3; 1Dept of Nutrition, Harvard Sch of Public Health, Boston, MA, 2MCI Rsch Div, Microclinic International, San Francisco, CA, 3Executive office, Microclinic International, San Francisco, CA, 4Executive Office, Microclinic International, San Francisco, CA
BACKGROUND: Obesity has been suggested to propagate within social networks. A social network program was engineered to contagiously propagate healthy lifestyles and leverage pre-existing social networks to decrease obesity. We expand upon a 9- to 10-month intervention program with 16 month followup to investigate the power of social networks in the first ever long-term randomized trial. METHODS: Based in rural Appalachian region of Kentucky, we investigate the Microclinic Social Network Behavioral Health Invervention (MSN) lifestyle intervention in a resource-limited but socially cohesive area with high obesity prevalence. Social clusters of 2-8 individuals who participated together in a program with weekly physical activity, nutrition, health education and social activity sessions led by health-educators; controls had access to standard care from local county health department. Body weight and waist circumference were collected in followup waves during intervention, plus at 16 months after baseline in a 52% sample subcohort. Longitudinal analyses utilized multilevel repeated-measures mixed models, with multilevels of neighborhood center, classroom, and social cluster (i.e. microclinic) to examine the change in health outcomes in program participants vs. controls. RESULTS: Study enrolled 552 participants, comprised of 242 social clusters, among 27 classroom clusters, and from 5 neighborhood cohorts. Participants were 85.8% women, mean age 50.9 years (13.8), mean BMI 36.2 (7.6). From baseline to end of intervention period, MSN intervention group showed decreased body weight of -6.52 lbs (95% CI: -8.57 to -4.47; P<0.001), and improved central adiposity with decreased waist circumference of -1.24 inches (-1.85 to -0.63; P<0.001), relative to controls. In subcohort at 16 months, decreases in weight (-4.70 lbs, -7.56 to -1.84) and waist circumference (-0.99 inches, -1.81 to -0.17) were maintained. CONCLUSIONS: Expanded and long-term findings demonstrate the effectiveness of Microclinic Social Network Behavioral Health Invervention for obesity control in resource limited settings. Results hold promise for socially engineering and leveraging the power of social networks interventions to propagate healthy lifestyle behaviors.
This research has received full or partial funding support from the American Heart Association.
Author Disclosures: E.L. Ding: None. K.T. Watson: None. N. Bui: None. L. Makarechi: None. L. Lang: None. M.R. Prescott: None. S.N. Safford: None. D. Banerjee: None. H.W. Campbell: None. J.A. Rushakoff: None. D.E. Zoughbie: None.
Key Words: Obesity; Behavior change; Behavioral aspects; Lifestyle; Epidemiology
Multifaceted Intervention to Improve Medication Adherence and Secondary Prevention Measures (Medication Study) After Acute Coronary Syndrome Hospital Discharge
Michael Ho1, Anne Lambert-Kerzner2, Evan Carey2, Ibrahim Fahdi3, Chris Bryson4, Dee S Melnyk5, Hayden Bosworth6, Tiffany Radcliff2, Casey Barnett7, Ryan Davis8, Howard Mun9, Jennifer Weaver7, Eric Del Giacco10; 1Medicine, VA Eastern Colorado Health Care System, Denver, CO, 2Rsch, VA Eastern Colorado Health Care System, Denver, CO, 3Medicine, Little Rock VA, Little Rock, AR, 4Medicine, Puget Sound VA Med Cntr, Seattle, WA, 5Pharmacy, Durham VA Med Cntr, Durham, NC, 6Rsch, VA Eastern Colorado Health Care System, Durham, NC, 7Pharmacy, Little Rock VA Med Cntr, Little Rock, AR, 8Pharmacy, VA Eastern Colorado Health Care System, Denver, CO, 9Pharmacy, Puget Sound VA Med Cntr, Denver, WA, 10Medicine, Little Rock VA Med Cntr, Little Rock, AR
Objective: Adherence to cardioprotective medications in the year after acute coronary syndrome (ACS) is poor. The objective of this study was to test a multi-faceted intervention to improve adherence to cardiac medications in the year after ACS hospital discharge. Design and Setting: Randomized controlled study at 4 VA Medical Centers. Participants: Two hundred fifty three patients admitted with ACS were randomized to intervention (INT) or usual care (UC) prior to hospital discharge. Intervention(s): The intervention comprised of: (1) pharmacist-led medication reconciliation and tailoring; (2) patient education; (3) collaborative care between pharmacist and primary care provider/cardiologist; and (4) 2 types of voice messaging (educational and medication refill reminder calls) and lasted for 1 year following hospital discharge. Main Outcome(s) and Measure(s): The primary outcome was proportion of patients adherent to medications based on mean proportion of days covered (PDC) >0.80 in the year after hospital discharge using pharmacy refill data for clopidogrel, beta-blockers, HMG CoA reductase inhibitors (statins), and angiotensin converting enzyme inhibitor (ACE)/angiotensin receptor blocker (ARB)). Secondary outcomes included achievement of blood pressure and low-density lipoprotein cholesterol targets. Results: Of 253 patients, 241 (95%) completed the study (122 in INT and 119 in UC). In the intervention group, 89.3% of patients were adherent compared to 73.9% in UC group (p=0.003). Mean PDC was higher in INT as well (0.94 vs. 0.87; INT vs. UC p=<0.001). A greater proportion of intervention patients were adherent to clopidogrel (87% vs. 71%; p=0.03), statins (93% vs. 82%; p<0.001), and ACE/ARB (93% vs. 82%; p=0.03) but not for beta-blockers (88% vs. 85%; p=0.59). There were no differences in achievement of BP and LDL goals. Conclusions and Relevance: A multifaceted intervention comprised of pharmacist-led medication reconciliation and tailoring, patient education, collaborative care between pharmacist and primary care provider/cardiologist, and voice messaging improved adherence to cardiac medications in the year after ACS hospital discharge. These findings may provide a framework to improve medication adherence.
Author Disclosures: M. Ho: None. A. Lambert-Kerzner: None. E. Carey: None. I. Fahdi: None. C. Bryson: None. D.S. Melnyk: None. H. Bosworth: None. T. Radcliff: None. C. Barnett: None. R. Davis: None. H. Mun: None. J. Weaver: None. E. Del Giacco: None.
Key Words: Adherence; Behavioral medicine; Outcomes; Acute coronary syndromes
China Rural Health Initiative - Sodium Reduction Study: the Effects of a Community-Based Sodium Reduction Program on 24hr Urinary Sodium and Blood Pressure in Rural China
Nicole Li1, Lijing Yan2, Wenyi Niu3, Chen Yao4, Xiangxian Feng5, Jianxin Zhang6, Jingpu Shi7, Yuhong Zhang8, Ruijuan Zhang9, Zhixin Hao2, Hongling Chu4, Jing Zhang10, Xian Li11, Zhifang Li12, Jixin Sun13, Bo Zhou7, Yi Zhao8, Yan Yu9, Darwin Labarthe14, Jixiang Ma15, Elizabeth Delong16, Paul Elliott17, Stephen MacMahon18, Yangfeng Wu19, Bruce Neal20; 1Food Policy, The George Institute for Global Health, Sydney, Australia; 2Rsch and Development, The George Institute for Global Health, China, Beijing, China; 3Sch of Public Health, Peking Univ Health Science Cntr, Beijing, China; 4Peking Univ Clinical Rsch Institute, Peking Univ Health Science Cntr, Beijing, China; 5Changzhi Med College, Changzhi Med College, Changzhi, China; 6Head Office, Hebei Province Cntr for Disease Prevention and Control, Shijiazhuang, China; 7Sch of Public Health, China Med Univ, Shenyang, China; 8Sch of Public Health, Ningxia Med Univ, Yinchuan, China; 9Dept of Public Health, Xi’an Jiaotong Univ, Xi'an, China; 10Rsch and Development, The George Institute for Global Health, China, Beijing, China; 11Data Management, The George Institute for Global Health, China, Beijing, China; 12Dept of Preventive Medicine, Changzhi Med College, Changzhi, China; 13Institute for Chronic Disease Prevention and Control, Hebei Province Cntr for Disease Prevention and Control, Shijiazhuang, China; 14Dept of Preventive Medicine, Northwestern Univ, Chicago, IL, 15Cntr for Chronic Disease Prevention and Control, Chinese Cntr for Disease Control and Prevention, Beijing, China; 16Sch of Medicine, Duke Univ, Durham, NC, 17Sch of Public Health, Imperial College Faculty of Medicine, London, Australia; 18Principal Director's Office, The George Institute for Global Health, Sydney, Australia; 19Executive Director, The George Institute for Global Health, China, Beijing, China; 20Senior Director, The George Institute for Global Health, Sydney, Australia
Background: Cardiovascular diseases are the leading cause of death in rural China. High blood pressure caused by excessive sodium consumption has been identified as an important modifiable risk factor. An effective low cost population-based strategy to reduce sodium intake in rural China has significant public health potential. Methods: The study is a large-scale, cluster-randomized trial done in five Northern provinces in China. Two counties have been selected from each province and 12 townships enrolled from each county making a total of 120 clusters. One village from each township was selected for participation and randomized to intervention or control with stratification by county. The 60 control group villages received no intervention and simply continued with their usual practices. The 60 intervention villages received general community health education advising reduced salt intake, specific health education targeting salt reduction messages to patients at high risk of cardiovascular diseases, and a food supply strategy designed to promote the sale of a reduced sodium added potassium salt substitute through the village convenience stores. The 60 intervention villages were further randomised into two equal groups, such that 30 villages had access to salt substitute at a price parity with normal salt and 30 had salt substitute available at market price (about twice the cost of normal salt). The intervention was implemented for 18 months. An age- and sex-stratified random sample of 2400 men and women from the 120 villages (20 from each village) were selected at the end of the intervention period for outcome evaluation. The primary outcome is 24-hour urinary sodium and secondary outcomes are blood pressure, 24 hour urinary potassium, urinary sodium:potassium ratio and the proportion with hypertension. Results Data have been collected as planned and are currently being analyzed. Results for the primary and secondary outcome measures will be reported. Conclusions: The study has successfully completed the implementation and evaluation of a novel, practical, scalable strategy for vascular disease prevention in rural China. The findings will have significant implications for health policy.
Author Disclosures: N. Li: None. L. Yan: None. W. Niu: None. C. Yao: None. X. Feng: None. J. Zhang: None. J. Shi: None. Y. Zhang: None. R. Zhang: None. Z. Hao: None. H. Chu: None. J. Zhang: None. X. Li: None. Z. Li: None. J. Sun: None. B. Zhou: None. Y. Zhao: None. Y. Yu: None. D. Labarthe: None. J. Ma: None. E. Delong: None. P. Elliott: None. S. MacMahon: None. Y. Wu: None. B. Neal: None.
Key Words: Community-based care; Health education; Blood pressure; Sodium; Cardiovascular disease prevention
Late-Breaking Clinical Trials: Medical and Surgical Approaches to Improving Heart Failure Outcomes
Atrial Antitachycardia Pacing and Managed Ventricular Pacing Reduce the Endpoint Composed by Death, Cardiovascular Hospitalizations and Permanent Atrial Fibrillation Compared to Conventional Dual Chamber Pacing in Bradycardia Patients: Results of the Minerva Randomized Study
Giuseppe Boriani1, Raymond Tukkie2, Lluis Mont3, Helmut Pürerfellner4, Antonis S Manolis5, Massimo Santini6, Giuseppe Inama7, Paolo Serra8, Silvia Parlanti9, Lorenza Mangoni9, Andrea Grammatico9, Luigi Padeletti10; 1Institute of Cardiology, Univ of Bologna, Policlinico S.Orsola-Malpighi, Bologna, Bologna, Italy; 2Institute of Cardiology, Kennemer Gasthuis, Haarlem, The Netherlands, Haarlem, Netherlands; 3Dept of Cardiology, Hosp Clinic, Univ of Barcelona, Spain, Barcelona, Spain; 4Dept of Cardiology, Akademisches Lehrkrankenhaus der Elisabethinen, Linz, Austria, Linz, Austria; 5First Dept of Cardiology, Evagelismos General Hosp, Athens, Greece, Athens, Greece; 6Cardiology Dept, S. Filippo Neri Hosp, Rome, Italy, Roma, Italy; 7Institute of Cardiology, Maggiore Hosp, Crema, Italy, Crema, Italy; 8Cardiology Dept, G. Mazzini Hosp, Teramo, Italy, Teramo, Italy; 9Regional Clinical Cntr, Medtronic Clinical Rsch Institute, Roma, Italy; 10Institute of Internal Medicine and Cardiology, Univ of Florence, Florence, Italy, Firenze, Italy
Background:Atrial fibrillation (AF) is a common comorbidity in bradycardia patients.The most advancedpacemakers feature atrial preventive pacing and atrial antitachycardia pacing (DDDRP), which may reduce AF occurrence and duration, and Managed Ventricular Pacing (MVP), which may minimize right ventricular pacing detrimental effects. We evaluated whether DDDRP and MVP might reduce mortality, morbidity or progression to permanent AF compared with standard dual-chamber pacing (Control DDDR). Methods: In a randomized parallel single-blind multi-center international trial weenrolled patients with bradycardia, previous atrial tachyarrhythmias and no history of permanent AF or third-degree atrioventricular block, in whom a DDDRP pacemaker had recently been implanted. Patients were randomly assigned in a 1:1:1 manner to Control DDDR, DDDRP+MVP or MVP. The primary outcome was the 2-year incidence of a combined endpoint composed of death, cardiovascular hospitalizations or permanent AF. Analysis was intention-to-treat using Kaplan-Meier estimates and log-rank test. Results: We randomized 1166 patients, aged 74±9 years, 588 (50%) males. The primary endpoint occurred in 102 of 385 Control DDDR patients (26.5%), in 76 of 383 DDDRP+MVP patients (19.8%) (hazard ratio 0.74, 95% confidence interval 0.55-0.99, p=0.04 vs. Control DDDR) and in 85 of 398 MVP patients (21.4%) (hazard ratio 0.89, 95% confidence interval 0.77-1.03, p=0.12 vs. Control DDDR), as shown in the figure. DDDRP+MVP was associated with a reduced risk of permanent AF (HR 0.39, 95% CI 0.21-0.75, p=0.004 vs. Control DDDR). Conclusions: In patients with bradycardia and atrial tachyarrhythmias, DDDRP+MVP is superior to standard dual-chamber pacing, as it reduces the endpoint composed of death, cardiovascular hospitalizations or permanent AF. The positive effect is mainly due to a decrease in the progression of atrial tachyarrhythmias to permanent AF.
Author Disclosures: G. Boriani: None. R. Tukkie: None. L. Mont: None. H. Pürerfellner: None. A.S. Manolis: None. M. Santini: Consultant/Advisory Board; Modest; Member of advisory boards for several device manufactures. G. Inama: None. P. Serra: None. S. Parlanti: Employment; Significant; Employee of Medtronic Inc. L. Mangoni: Employment; Significant; Employee of Medtronic Inc. A. Grammatico: Employment; Significant; Employee of Medtronic Inc. L. Padeletti: Speakers Bureau; Modest; Speaker for several device manufactures. Consultant/Advisory Board; Modest; Member of advisory boards for several device manufactures.
Key Words: Atrial fibrillation; Pacemakers; Pacing
Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE AHF) Trial
Horng H Chen1, Barry A Borlaug1, Kevin J Anstrom2, G. M Felker3, Michael M Givertz4, Anita Deswal5, Bradley A Bart6, Lynne W Stevenson4, Jean L Rouleau7, Eileen O'Meara8, Martin M LeWinter9, David A Bull10, Josef Stehlik10, Marc J Semigran11, Steven R Goldsmith6, Elizabeth O Ofili12, Christopher M O'Connor13, W.H. Wilson Tang14, Randall C Starling14, Javed Butler15, David J Whellan16, Kenneth B Margulies17, Thomas P Cappola17, Marvin A Konstam18, Douglas L Mann19, Victor Davila-Roman19, Steven E McNulty2, Eric J Velazquez13, Kerry L Lee2, Monica R Shah20, Adrian F Hernandez2, Eugene Braunwald4, Magaret M Redfield1; 1Internal medicine, MAYO Clinic, Rochester, MN, 2Duke Clinical Rsch Institute, Duke Clinical Rsch Institute, Durham, NC, 3Duke Heart Cntr, Duke Univ Sch of Medicine, Durham, NC, 4Internal medicine, Brigham and Women’s Hosp, Boston, MA, 5Internal medicine, Baylor College of Medicine & Baylor Clinic, Houston, TX, 6Internal medicine, Univ of Minnesota, Minneapolis, MN, 7Internal medicine, Univ of Montreal/Montreal Heart Institute, Montreal, Canada; 8Montreal Heart Institute, Univ of Montreal/Montreal Heart Institute, Montreal, Canada; 9Internal medicine, Univ of Vermont, Burlington, VT, 10Internal medicine, Univ of Utah Health Sciences Cntr, Salt Lake City, UT, 11Internal medicine, Massachusetts General Hosp, Boston, MA, 12Internal medicine, Morehouse Sch of Medicine, Atlanta, GA, 13Internal medicine, Duke Univ Sch of Medicine and Duke Heart Cntr, Durham, NC, 14Internal medicine, Cleveland Clinic, Cleveland, OH, 15Internal medicine, Emory Univ, Atlanta, GA, 16Internal medicine, Thomas Jefferson Univ, Philadelphia, PA, 17Internal medicine, Univ of Pennsylvania, Philadelphia, PA, 18Internal medicine, Tufts Univ Sch of Medicine, Boston, MA, 19Internal medicine, Washington Univ, St Louis, MO, 20NHLBI, NHLBI, Bethesda, MD
BACKGROUND:Worsening renal function and inadequate decongestion during acute heart failure (AHF) treatment are each associated with worse outcomes. Small studies suggest that low dose dopamine or low dose nesiritide may preserve renal function and improve decongestion in AHF. HYPOTHESES: As compared to placebo, the addition of low dose dopamine (2 ug/kg/min) or low dose nesiritide (0.005 ug/kg/min without bolus) to optimal diuretic dosing will enhance renal function and decongestion in AHF. The ROSE AHF study uses a novel study design to address these two independent hypotheses (Figure). METHODS:ROSE AHF (NCT01132846) is a multicenter, double-blind, placebo controlled, randomized clinical trial conducted within the NHLBI-sponsored Heart Failure Research Network. Patients (n=360) hospitalized for AHF who have renal dysfunction (glomerular filtration rate (GFR) of 15 to 60 mL/min/1.73m2) were enrolled within 24 hours of admission. The co-primary endpoints are the change in serum cystatin-C (renal function) from baseline to 72 hours and the 72-hour cumulative urine volume (decongestion). The study design utilizes sequential randomization and a pooled placebo group. The dopamine and nesiritide groups will each be compared to the pooled placebo group. With 120 patients per treatment arm, ROSE AHF has 85% power to detect a treatment difference of 0.3 mg/L in serum cystatin C and 90% power to detect a treatment difference of > 1400 mL in cumulative 72 hour urine volume with dopamine or with nesiritide. All statistical analyses are pre-specified, two-sided and based on intention to treat. RESULTS:Enrollment and primary follow-up are completed. Median age of the 360 patients (27% female) is 70 years with 67% having ≥ 1 HF hospitalization within the last year. CONCLUSION:The results of the ROSE AHF trial will determine whether adding either of these two clinically available therapies to optimal diuretic dosing preserves renal function and/or enhances decongestion in AHF.
Author Disclosures: H.H. Chen: Research Grant; Significant; Sciso Inc. Ownership Interest; Significant; Zumbro Discovery Inc. Other; Modest; Royalties Niles therapeutics, Anexon Inc and Up-to date, Patent Chimeric natriuretic peptides. B.A. Borlaug: None. K.J. Anstrom: None. G.M. Felker: Research Grant; Modest; Novartis, Amgen, Otsuka & Roche Diagnostics. Consultant/Advisory Board; Modest; Novartis, Amgen & Roche Diagnostics. M.M. Givertz: Consultant/Advisory Board; Significant; Merck, Cardioxyl, Janssens. A. Deswal: None. B.A. Bart: None. L.W. Stevenson: None. J.L. Rouleau: None. E. O'Meara: None. M.M. LeWinter: None. D.A. Bull: None. J. Stehlik: None. M.J. Semigran: None. S.R. Goldsmith: None. E.O. Ofili: None. C.M. O'Connor: None. W. Tang: None. R.C. Starling: None. J. Butler: None. D.J. Whellan: Consultant/Advisory Board; Modest; Novartis. Research Grant; Significant; Medtronic Inc, Pozen, Johnson & Johnson, REsMed, NHLBI. Consultant/Advisory Board; Significant; Viamet, Terumo, Pozen, ResMed. K.B. Margulies: None. T.P. Cappola: None. M.A. Konstam: None. D.L. Mann: None. V. Davila-Roman: None. S.E. McNulty: None. E.J. Velazquez: None. K.L. Lee: None. M.R. Shah: None. A.F. Hernandez: Honoraria; Modest; Corthera. Consultant/Advisory Board; Modest; Janssen. E. Braunwald: Research Grant; Significant; DCRI and Johnson & Johnson. Honoraria; Modest; Bayer. M.M. Redfield: Other; Modest; Royalties Anexon Inc.
Key Words: Acute heart failure; Renal function; Cardiovascular therapeutics; Catecholamines; Natriuretic peptide
Severe Ischemic Mitral Regurgitation: Is it Better to Repair or Replace the Valve?
Michael A Acker1, Michael K Parides2, Louis P Perrault3, Alan J Moskowitz2, Pierre Voisine4, Peter K Smith5, Annetine C Gelijns2, Judy W Hung6, Eugene Blackstone7, John Puskas8, Michael Argenziano9, James S Gammie10, Michael Mack11, Deborah D Ascheim2, Emilia Bagiella2, T. Bruce Ferguson12, Keith Horvath13, Nancy L Geller14, Marissa A Miller14, Joseph Y Woo15, David A D'Alessandro16, Gorav Ailawadi17, François Dagenais18, Timothy J Gardner19, Patrick T O'Gara20, Robert Michler21, Irving L Kron22; 1Div of Cardiovascular Surgery, Hosp of the Univ of Pennsylvania, Philadelphia, PA, 2Health Evidence and Policy, Icahn Sch of Medicine at Mount Sinai, New York, NY, 3Cardiac Surgery, Montreal Heart Institute, Montreal, Canada; 4Div of Cardiac Surgery, INSTITUT UNIVERSITAIRE DE CARDIOLOGIE DE QUEBEC, Quebec, Canada; 5Surgery/Cardiovascular & Thoracic, Duke Univ, Durham, NC, 6Echocardiography Core Lab, Massachusetts General Hosp, Boston, MA, 7Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland, OH, 8Cardiothoracic Surgery, Emory Univ Hosp Midtown, Atlanta, GA, 9Minimally Invasive Cardiac Surgery and Arrhythmia Surgery, Columbia Univ Med Cntr, New York, NY, 10Div of Cardiac Surgery, Univ of Maryland, Baltimore, MD, 11Cardiovascular Services, BAYLOR RESEARCH INSTITUTE, Plano, TX, 12Cardiovascular Sciences, East Carolina Heart Institute at ECU, Greenville, NC, 13Cardiothoracic Surgery, NIH Heart Cntr at Suburban Hosp, Bethesda, MD, 14National Heart Lung and Blood Insititute, National Institutes of Health, Bethesda, MD, 15Div of Cardiothoracic Surgery, Hosp of the Univ of Pennsylvania, Philadelphia, PA, 16Cardiothoracic Surgery, Montefiore-Einstein Heart Cntr, Bronx, NY, 17Cardiothoracic Surgery, Univ of Virginia Health System, Charlottesville, VA, 18Dept of Cardiology, INSTITUT UNIVERSITAIRE DE CARDIOLOGIE DE QUEBEC, Quebec, Canada; 19cardiovascular medicine, Christiana Care Health System, Newark, DE, 20Clinical Cariology, Brigham and Women's Hosp, Boston, MA, 21Cardiovascular and Thoracic Surgery, Montefiore-Einstein Heart Cntr, Bronx, NY, 22Surgery, Univ of Virginia Health System, Charlottesville, VA
BACKGROUND: Ischemic mitral regurgitation (MR), which develops as a complication of myocardial infarction and adverse left ventricular remodeling, is associated with significant mortality risk over time. Practice guidelines recommend repair or replacement for severe, ischemic MR, but there remains a lack of conclusive evidence to indicate which of these interventions is superior. The choice between these surgical options is characterized by the trade-off between reduced operative morbidity and mortality with repair versus better long-term correction of ischemic MR with replacement. The long-term benefits of repair versus replacement remain unknown, which has led to uncertainty and significant variation in surgical practice. METHODS: The severe MR (SMR) randomized trial was designed to evaluate the safety and effectiveness of mitral valve repair versus replacement in patients with severe ischemic MR. This trial is being conducted as part of the NIH and CIHR supported Cardiothoracic Surgical Trials Network (CTSN) in 22 clinical centers. The primary endpoint for the trial is the degree of left ventricular remodeling, as assessed by Left Ventricular End Systolic Volume Index (LVESVI) at 12 mos post-surgery by TTE (integrative method). Secondary endpoints include mortality, MACE, adverse events, recurrent MR, QoL, and hospitalizations (24 mos). RESULTS The patient population consists of 251 patients with severe ischemic MR (often with tethering as a major mechanism) with and without need for CABG (table). The mean baseline LVESVI was 63.4 (±26.8). The average follow-up time of the cohort is 19 months as of 6/18/13 and all patients have recently completed their one-year endpoint assessment. Primary and secondary endpoint data will be presented. CONCLUSIONS: The approach to managing ischemic MR remains controversial. The results of the trial will help delineate the appropriate therapeutic approach for this growing patient population.
Author Disclosures: M.A. Acker: Consultant/Advisory Board; Modest; Thoratec Inc. M.K. Parides: None. L.P. Perrault: None. A.J. Moskowitz: None. P. Voisine: None. P.K. Smith: None. A.C. Gelijns: None. J.W. Hung: None. E. Blackstone: None. J. Puskas: None. M. Argenziano: None. J.S. Gammie: None. M. Mack: None. D.D. Ascheim: Consultant/Advisory Board; Modest; Backbeat Medical, Inc., Velomedix. E. Bagiella: None. T. Ferguson: None. K. Horvath: None. N.L. Geller: None. M.A. Miller: None. J.Y. Woo: None. D.A. D'Alessandro: None. G. Ailawadi: Research Grant; Significant; Astra Zeneca ( investigation of aneurysms). Speakers Bureau; Modest; St. Jude speaker, Atricure proctor. Consultant/Advisory Board; Modest; Abbott, Edwards. F. Dagenais: None. T.J. Gardner: Other; Modest; Chair, Steering Committee, Cardiothoracic Surgical Trials Network, NHLBI. P.T. O'Gara: None. R. Michler: None. I.L. Kron: None.
Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT)
Marc A Pfeffer1, Sonja McKinlay2, Bertram Pitt (for the TOPCAT Investigators)3; 1Medicine, Brigham & Women's Hosp, Harvard, Boston, MA, 2CTCC, New England Rsch Institute, Watertown, MA, 3Medicine, Univ of Michigan Med Cntr, Ann Arbor, MI
Introduction In the absence of a proven therapy to improve the prognosis of patients with heart failure and preserved LV ejection fraction (HFpEF) treatment remains empirical. Mineralocorticoid receptor antagonists have been shown to reduce the risk of death and other major cardiovascular events in patients with reduced EF heart failure and following myocardial infarction. Hypothesis Treatment Of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) is a NHLBI contract, international randomized placebo controlled trial evaluating the effectiveness and safety of spironolactone (15mg titrated to 45mg) compared to placebo in patients with HFpEF, using time to first event cardiovascular mortality, aborted cardiac arrest, or heart failure hospitalization as the primary endpoint. Methods Inclusion criteria were informed consent, age ≥ 50 years, symptomatic HF, LVEF ≥ 45%, HF hospitalization (within 12 months, Stratum I) or an elevated BNP or NT proBNP (≥100 or 360 pg/ml, Stratum II). Recent stroke, coronary event, uncontrolled hypertension, eGFR < 30, and hyperkalemia (≥5.0 mmol/L) were some of the major exclusions. Subjects were randomized within each stratum and followed for 3.4 years on average. Safety assessments, nonfatal cardiovascular events, the development of atrial fibrillation, diabetes mellitus and quality of life were key secondary endpoints. Results There were 3445 participants, 2480 and 965 in stratum I and II, respectively with country totals: USA 1151, Russia 1066, Republic of Georgia 612, Canada 326, Brazil 167 and Argentina 123. TOPCAT subjects were 68.6 ± 9.6 years old, 52% female, 63% NYHA II, 33% NYHA III and had a mean LVEF 57±7%. Baseline comorbidities included hypertension 91%; coronary artery disease 59%; chronic kidney disease 38%; atrial fibrillation 35%; and diabetes mellitus 32%. Key baseline measures were: Blood Pressure 129±14/76±11 mmHg; Heart Rate 69±10/min; BMI 32.1±7.3 kg/m2; eGFR 67.7±20.1 mL/min /1.73m2; Median Urine Microalbumin 20.0 IQR (7.0, 88.4) mg/g creatinine. ConclusionThe Data Safety Monitoring Committee allowed the trial to complete follow-up uninterrupted. This AHA submission represents the first public presentation of the TOPCAT trial RESULTS: NCT00094302
Author Disclosures: M.A. Pfeffer: Research Grant; Significant; Amgen, Celladon, Novartis, Sanofi-Aventis. Consultant/Advisory Board; Modest; Aastrom, Amgen, Bristol-Myers Squibb, Cerenis, Concert, Genzyme, Hamilton Health Sciences, Keryx, Medtronic, Merck, Novartis, Roche, Servier, University of Oxford and Xoma. Consultant/Advisory Board; Significant; Teva. Other; Modest; Brigham & Women’s Hosp has patents for use of inhibitors of the RAS in selected survivors of MI. Dr. Pfeffer’s share of the licensing agreement with Novartis is irrevocably transferred to charity. S. McKinlay: None. B. Pitt (for the TOPCAT Investigators): Consultant/Advisory Board; Modest; Pfizer, Bayer, Merck, Novartis, Takeda, Bristol-Myers Squibb, Astra Zeneca, BG-Medicine and Relypsa. Other; Modest; Equity Interests in BG-Medicine and Relyspa.
Key Words: Heart failure; Clinical trials
Late-Breaking Clinical Trials: Therapeutic Advances in Coronary and Peripheral Vascular Disease
One Year Mortality in STEMI Patients Randomized to Primary PCI or a Pharmaco-invasive Strategy. The Stream 1 Year Follow-up
Peter Sinnaeve1, Paul Armstrong2, Anthony Gershlick3, Patrick Goldstein4, Robert Wilcox5, Thierry Danays6, Louis Soulat7, Katleen Vandenberghe1, Anne Regelin8, Kris Bogaerts9, Frans Van de Werf1; 1Departement of Cardiovascular Sciences, Univ of Leuven, Leuven, Belgium; 2the Canadian Virtual Coordinating Cntr for Global Collaborative Cardiovascular Rsch, Univ of Alberta, Edmonton, Canada; 3Leicester Cardiovascular Biomedical Rsch Unit, National Institute for Health Rsch, Leicester, United Kingdom; 4SAMU, Lille Univ Hosp, Lille, France; 5Dept of Cardiovascular Medicine, Univ of Nottingham, Nottingham, United Kingdom; 6Boehringer Ingelheim, Reims, France; 7Service des Urgences, Cntr Hospier, Chateauroux, France; 8Boehringer Ingelheim, Basel, Switzerland; 9Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Univ of Leuven and Univ Hasselt, Leuven, Belgium
In the STREAM trial 1892 STEMI patients presenting within 3 hours after onset of symptoms and unable to undergo primary PCI within 1 hour were randomized to a pharmaco-invasive (PI) strategy or standard primary PCI according to local practice. The PI approach consisted of bolus tenecteplase (TNK), clopidogrel and enoxaparin with dose adjustments in the elderly. The primary combined endpoint of death, shock, congestive heart failure and reinfarction at 30 days was nominally lower in PI patients (12.4% vs 14.3%, p=0.21). The incidence of congestive heart failure (6.1% vs 7.6%, p=0.18) and shock (4.4% vs 5.9%, p=0.13) were also lower and more aborted infarction (11.1% vs 6.9%,p<0.01) were observed in PI patients, suggesting more salvage of ischemic myocardium due to earlier reperfusion (the median times between symptom onset and bolus tenecteplase or start of PCI procedure were 100 and 178 min, respectively; p<0.001). PI patients were also more likely to undergo CABG than patients allocated to primary PCI (4.7% vs 2.1%, p=0.002) potentially due to avoidance of urgent PCI in about one third of PI patients, whereas because of successful reperfusion, coronary angiography could be performed non-urgently in the remainder. As pre-specified by protocol, one year mortality data were acquired in all patients surviving the first 30 days. The last patient was randomized on July 26, 2012; the database was locked on September 30, 2013 and survival plus rehospitalization data are available on 1877 patients (< 0.8% lost to follow-up).
Author Disclosures: P. Sinnaeve: Speakers Bureau; Modest; Boehringer Ingelheim, Bayer, Pfizer, BMS. Honoraria; Modest; Johnson & Johnson (Bayer). P. Armstrong: Consultant/Advisory Board; Modest; Eli Lilly. Other; Modest; Unrestricted educational grant from AstraZeneca Eli Lilly. Research Grant; Significant; Boehringer Ingelheim, Hoffmann LaRoche, sanofi aventis. A. Gershlick: Honoraria; Modest; Boehringer Ingelheim. Other; Modest; Boehringer Ingelheim (travel). P. Goldstein: Speakers Bureau; Modest; AstraZeneca, Boehringer Ingelheim, Daiichi Lilly, The Medicine Company. Honoraria; Modest; Boehringer Ingelheim, Daiichi Lilly, The Medicine Company, AstraZeneca. Consultant/Advisory Board; Modest; Boehringer Ingelheim, Daiichi Lilly, Sanofi, Astra zeneca, Bayer, The Medicine Company. R. Wilcox: Honoraria; Modest; Boehringer Ingelheim. T. Danays: Employment; Significant; Boehringer Ingelheim. L. Soulat: Speakers Bureau; Modest; Lilly, The Medicine Company. Consultant/Advisory Board; Modest; Lilly, The Medicine Company. Other; Modest; Boehringer Ingelheim (Investigator STREAM). K. Vandenberghe: Research Grant; Significant; Boehringer Ingelheim. Other; Modest; Boehringer Ingelheim (travel). A. Regelin: Employment; Significant; Boehringer Ingelheim. K. Bogaerts: Consultant/Advisory Board; Modest; Boehringer Ingelheim. Other; Modest; Boehringer Ingelheim (travel). F. Van de Werf: Speakers Bureau; Modest; Boehringer Ingelheim. Honoraria; Modest; Boehringer Ingelheim. Research Grant; Significant; Reasearch grant from BI to perform STREAM.
Key Words: Myocardial infarction, STEMI; Fibrinolytic agents; Percutaneous coronary intervention
Secretory Phospholipase A2 Inhibition with Varespladib and Cardiovascular Events in Patients with an Acute Coronary Syndrome: Results of the VISTA-16 Study
Stephen Nicholls1, John J Kastelein2, Danielle Brennan3, Gregory G Schwartz4; 1Heart Health Theme, South Australian Health and Med Rsch Institute, Adelaide, Australia; 2Vascular Medicine, Academic Med Cntr, Amsterdam, Netherlands; 3Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, 4Cardiology, VA Med Cntr and Univ of Colorado Sch of Medicine, Denver, CO
Background: Secretory phospholipase A2 (sPLA2) may act upon lipoprotein phospholipids to generate bioactive products implicated in the progression of atherosclerosis. While sPLA2 inhibition with varespladib has a favorable effect on lipid and inflammatory markers, its impact on cardiovascular outcomes is unknown. Methods: 5,012 patients with an acute coronary syndrome were randomly assigned to receive treatment with varespladib 500 mg or placebo for 16 weeks, in addition to atorvastatin and other established therapies. The primary efficacy endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and unstable angina with evidence of ischemia requiring hospitalization. Results: At a pre-specified interim analysis the independent Data Safety Monitoring Board recommended termination of the trial for futility. At the time of study closure, primary endpoints occurred in 5.9% of patients treated with varespladib, versus 4.7% of patients treated with placebo (hazard ratio 1.24, 95% CI 0.95-1.63, P=0.11). Varespladib was associated with a greater risk of non-fatal myocardial infarction (cumulative incidence 3.3% versus 2.1%, hazard ratio 1.69, 95% CI 1.14-2.50, P=0.008). Complete data for all patients will be presented. Conclusion: In patients with recent acute coronary syndrome, varespladib did not reduce the risk of recurrent cardiovascular events. Rather, a greater risk of myocardial infarction indicates a potential adverse effect of sPLA2 inhibition with varespladib.
Author Disclosures: S. Nicholls: Research Grant; Significant; Anthera, AstraZeneca, Roche, Resverlogix, Novartis, Amgen, Eli Lilly. Consultant/Advisory Board; Modest; AstraZeneca, Roche, Omthera, Novartis, Eli Lilly, Merck, Roche, Takeda, CSL Behring, Boehringer Ingelheim. J.J. Kastelein: Consultant/Advisory Board; Modest; Anthera, The Medicines Company, CSL Behring, Resverlogix, Boehringer Ingelheim, Roche, Kinemed, Eli Lilly, MSD, Cerenis, Esperion, Novartis and Dezima Pharmaceuticals. D. Brennan: None. G.G. Schwartz: None.
Key Words: Arteriosclerosis; Inflammation; Acute coronary syndromes; Clinical trials
Randomized Comparison of Endovascular Revascularization Plus Supervised Exercise Therapy Versus Supervised Exercise Therapy Only in Patients With Peripheral Artery Disease and Intermittent Claudication: Results of the Endovascular Revascularization and Supervised Exercise (ERASE) Trial
Farzin Fakhry, Myriam G Hunink; Epidemiology, Erasmus MC, Rotterdam, Netherlands
Background: Intermittent claudication is the most common presentation of peripheral artery disease, associated with significant functional disability. Currently, supervised exercise therapy (SET) is being recommended as first-line treatment for intermittent claudication. However, a combination therapy of endovascular revascularization (EVR) plus SET seems more promising but has not been properly investigated in a large randomized trial. We instigated the ERASE trial to compare the clinical effectiveness of EVR plus SET versus the standard care of SET only in patients with intermittent claudication. Methods: In a multicenter randomized controlled trial 212 patients with claudication were randomly assigned to receive either a combination therapy of EVR plus SET (n=106) or SET only (n=106). All patients had a clinical and quality of life assessment before intervention and at 1, 6 and, 12 months follow-up. Functional performance measures including pain-free and maximum walking distance were recorded during a graded treadmill test. The VascuQol and Short-Form 36 Health Survey (SF-36) were used to assess the patient reported health-related quality of life. Repeated measurement techniques were used to analyze the data on an intention to treat basis. Results: After 12 months the completeness of follow-up was 94% in the combination therapy group and 92% in the SET group. At 12 months, compared to SET, the combination therapy was associated with a 282 meters (99% CI, 60 to 505 meters; P=0.001) greater improvement in maximum walking distance and a 408 meters (99% CI, 195 to 622 meters; P <0.001) greater improvement in pain-free walking distance. Similarly, the disease specific VascuQol showed greater improvement in the combination therapy group (mean difference 0.62; 99% CI, 0.20 to 1.03; P <0.001). Moreover, the SF-36 scale Physical Functioning was associated with significantly greater improvement in the combination therapy group compared to the SET group (P=0.002). Conclusions: After 12 months, in patients with intermittent claudication a combination therapy of EVR followed by SET resulted in significant greater improvements in pain-free and maximum walking distance and health-related quality-of-life scores compared to the standard care of SET only.
Author Disclosures: M.G. Hunink: None.
Key Words: Peripheral arterial disease; Angioplasty; Rehabilitation; Comparative effectiveness; Quality of life
A Randomized Multicenter Clinical Trial of Renal Artery Stenting in Preventing Cardiovascular and Renal Events: Results of the CORAL Study
Christopher J Cooper1, Timothy P Murphy2, Donald E Cutlip3, Ralph D'Agostino4, Kenneth Jamerson5, Alan H Matsumoto6, Michael R Jaff7, Steffes Michael8, Scott Solomon9, David Cohen10, Katherine R Tuttle11, John H Rundback12, Joseph I Shapiro13, Diane Reid14, William Henrich15, Lance Dworklin16; 1Medicine, Univ of Toledo, Toledo, OH, 2Radiology, Rhode Island Hosp/Brown Univ Med Sch, Providence, RI, 3Medicine, Beth Israel Deaconnes Hosp/Harvard Med Sch, Boston, MA, 4Mathematics & Statistics, Boston Univ, Boston, MA, 5Medicine, Univ of Michigan Med Cntr/Univ of Michigan, Ann Arbor, MI, 6Radiology and Med Imaging, Univ of Virginia, Charlottesville, VA, 7Medicine, Massachusetts General Hosp, Boston, MA, 8Laboratory Medicine and Pathology, Univ of Minnesota, Minneapolis, MN, 9Non-Invasive Cardiac Laboratory, Brigham and Women's Hosp, Boston, MA, 10Cardiology, Mid-America Heart Institute, Kansas City, MO, 11Medicine, Providence Med Rsch Cntr, Spokane, WA, 12Interventional Institute, Institute of Clinical Rsch, Teaneck, NJ, 13Medicine, Marshall Univ, Huntington, WV, 14Div of Heart and Vascular Diseases, National Heart Lung & Blood Institute, Bethesda, MD, 15Medicine, Univ of Texas HSC at San Antonio, San Antonio, TX, 16Medicine, Rhode Island Hosp/Brown Univ. Med Sch, Providence, RI
Introduction: Atherosclerotic renal artery stenosis is a common problem for which there is no clear consensus on treatment. Objective: To examine whether patients with atherosclerotic renal artery stenosis, accompanied by systolic hypertension and/or chronic kidney disease, have fewer clinical events after stent revascularization plus optimal medical therapy than when treated with optimal medical therapy alone. Methods: Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) is a randomized, multi-centered, NIH-sponsored, international clinical trial. The primary entry criteria were 1) an atherosclerotic renal stenosis ≥60% and 2) hypertension on ≥ 2 anti-hypertensive medications and or ≥ stage 3 chronic kidney disease. The trial was powered to detect a 25% difference in the primary composite endpoint: first occurrence of cardiovascular or renal death, myocardial infarction, hospitalization for heart failure, stroke, 30% reduction in GFR, or need for renal replacement therapy. Results: In CORAL 947 subjects were randomly allocated to stent plus medical therapy or medical therapy alone and followed for 2 to 7.5 years for the occurrence of the primary endpoint composite. The population was 50% female with a mean age 69±9 years. On entry, their average systolic blood pressure was150±23 mmHg and mean GFR, 58±22 ml/min. The proportion of subjects with Stage 4 or greater CKD was 7.5%. Diabetes mellitus was present in 34%, and congestive heart failure in 13%. The mean percent diameter stenosis was 67±11% by core lab analysis. The results of the primary endpoint analysis will be presented. Conclusion: The pivotal data from CORAL, the first randomized trial of renal artery intervention designed to test prevention of clinical events, will be presented.
Author Disclosures: C.J. Cooper: Research Grant; Significant; Cordis, AstraZeneca, Pfizer. T.P. Murphy: Research Grant; Modest; Cordis, Abbott Vascular. D.E. Cutlip: Research Grant; Modest; Medtronic, Boston Scientific, Abbott Vascular. R. D'Agostino: None. K. Jamerson: None. A.H. Matsumoto: Research Grant; Modest; WL Gore, Medtronic, Cook. Ownership Interest; Modest; Volcano. Consultant/Advisory Board; Modest; Medicines Co., Boston Scientific,. Other; Modest; Trivascular, Bolton Medical, WL Gore. M.R. Jaff: Ownership Interest; Modest; Northwind Medical, PQ Bypass, Access Closure, Hotspur, ICON Interventional, MC 10, Sadra Medical, Sano V, Vascular Therapies. Consultant/Advisory Board; Modest; Abbott Vascular, Cordis Corporation, Covidien Vascular, Medtronic Vascular, Astra Zeneca, Boston Scientific, Trivascular. Ownership Interest; Significant; Primacea, Embolitech, Janacare. Consultant/Advisory Board; Significant; American Genomics. Other; Significant; Board Member, VIVA Physicians, a 501 c 3 not-for-profit education and research organization. S. Michael: None. S. Solomon: None. D. Cohen: Research Grant; Significant; Medtronic, Abbott Vascular, Boston Scientific, Covidien. Consultant/Advisory Board; Modest; Medtronic, Abbott Vascular. K.R. Tuttle: None. J.H. Rundback: Consultant/Advisory Board; Modest; St Judes, EV3/Covidien, Biotronik, Simbionix, Boston Scientific, Ekos, VIVA Vascular Physicians. J.I. Shapiro: None. D. Reid: None. W. Henrich: None. L. Dworklin: None.
Key Words: Renal circulation; Stent; Clinical trials
Late-Breaking Clinical Trials: New Strategies for Atrial Fibrillation Patients: Rhythm and Thrombosis
RADAR-AF Trial. A Randomized Multicenter Comparison of Radiofrequency Catheter Ablation of Drivers versus Circumferential Pulmonary Vein Isolation in Patients with Atrial Fibrillation
Felipe Atienza1, José M Ormaetxe2, Angel Moya3, Txules Martínez-Alday4, Antonio Hernandez-Madrid5, Eduardo Castellanos6, Fernando Arribas7, Miguel A Arias6, Luis Tercedor8, Rafael Peinado9, Nieves Martinez-Alzamora10, Jesus Almendral11, José Jalife12; 1Cardiology, Hosp Gregorio Maranon, Madrid, Spain; 2Cardiology, Hosp de Basurto, Bilbao, Spain; 3Cardiology, Hosp Vall d′Hebron, Barcelona, Spain; 4Cardiology, Clinica San Sebastian, Bilbao, Spain; 5Cardiology, Hosp Ramón y Cajal, Madrid, Spain; 6Cardiology, Hosp Virgen de la Salud, Toledo, Spain; 7Cardiology, Hosp Doce de Octubre, Madrid, Spain; 8Cardiology, Hosp Virgen de las Nieves, Granada, Spain; 9Cardiology, Hosp La Paz, Madrid, Spain; 10Statistics and Operative Rsch, Universidad Politecnica de Valencia, Valencia, Spain; 11Cardiology, Hosp Monteprincipe, Madrid, Spain; 12Cardiology, Univ of Michigan, Ann Arbor, MI
Background: Empiric circumferential pulmonary vein isolation (CPVI) has become therapy of choice for drug-refractory atrial fibrillation (AF). However, results are yet suboptimal and the outcomes of a mechanistically-based strategy aimed at targeting AF drivers is unknown. Objective: This multi-center, single blinded, randomized clinical trial (Clin. Trials. Gov. NCT00674401) was designed to compare the efficacy and safety of high frequency source ablation (HFSA) in AF. Methods: In paroxysmal AF (PaAF), pts were randomized to undergo CPVI or HFSA only using a noninferiority design. In persistent AF (PeAF), pts were randomized to CPVI or to a combined ablation approach (CPVI+HFSA) using a superiority design. The primary endpoint was freedom from AF at 6 months post-first ablation procedure off antiarrhythmic medications. Secondary endpoints included freedom from AF and from AT/AF at 6 and 12 months post-ablation off/on antiarrhythmic medications and incidence of complications. All analyses were intention-to-treat. Pts were followed by ECG and 48-hour Holter at 3&6&12 mo. Results: Two hundred thirty two pts (mean age 53±10 years, 186 males), PaAF (115) or PeAF (117). Baseline characteristics were similar between groups. In PaAF, HFSA was noninferior to CPVI at 12 months for the freedom from AF and AT/AF endpoint (Figure). There was a significant reduction of the risk difference of severe adverse events in the HFSA vs. CPVI group (p=0.03). In PeAF, there were no significant differences between treatment groups in the primary (60% vs 61%; p=ns) and secondary endpoints, and a trend towards an increase in severe adverse events rate (24% vs 10%; p=0.08) in the combined group. Conclusions: In PaAF patients, HFSA was noninferior to CPVI at 12 months to achieve freedom of AT/AF, with a lower incidence of severe adverse events. In PeAF, the addition of HFSA to CPVI offered no incremental value. These results offer a novel mechanistic treatment paradigm for PaAF.
Author Disclosures: F. Atienza: Research Grant; Modest; St Jude Medical Spain. Consultant/Advisory Board; Modest; Medtronic, Boston Scientific. J.M. Ormaetxe: None. A. Moya: None. T. Martínez-Alday: None. A. Hernandez-Madrid: None. E. Castellanos: None. F. Arribas: None. M.A. Arias: None. L. Tercedor: None. R. Peinado: None. N. Martinez-Alzamora: None. J. Almendral: None. J. Jalife: Ownership Interest; Significant; Topera, Inc., Rhythm Solutions, Inc., Avert AF.
Key Words: Ablation, radiofrequency; Atrial fibrillation; Outcomes; Arrhythmia mapping; Arrhythmias, treatment of
A Randomized Trial Comparing Genotype-Guided Dosing of Warfarin to Standard Dosing: The EU Pharmacogenetics of Anticoagulant Therapy (EU-PACT) Warfarin Study
Munir Pirmohamed1, Girvan Burnside2, Jenni Stoddern3, Clare Prince3, Cheng Hok Toh4, Toby Nicholson5, Patrick Kesteven6, Andrea Jorgensen7, Ann Daly8, Anke-Hilse Maitland-van der Zee9, Paula Williamson2, Niclas Eriksson10, Peter Avery11, Farhad Kamali12, Mia Wadelius13; 1Molecular and Clinical Pharmacology, Univ of Liverpool, Liverpool, United Kingdom; 2Biostatistics, Univ of Liverpool, Liverpool, United Kingdom; 3Pharmacology, Univ of Liverpool, Liverpool, United Kingdom; 4Haematology, Univ of Liverpool, Liverpool, United Kingdom; 5Haematology, Whiston Hosp, Prescot, United Kingdom; 6Haematology, Royal Victoria Infirmary, Newcastle, United Kingdom; 7Biostastics, Univ of Liverpool, Liverpool, United Kingdom; 8Institute of Cellular Medicine, Newcastle Univ, Newcastle Upon Tyne, United Kingdom; 9Utrecht Institute for Pharmaceutical Sciences, Utrecht Univ, Uetrecht, Netherlands; 10Biostatistics, Uppsala Clinical Rsch Cntr, Uppsala, Sweden; 11Sch of Mathematics & Statistics, Newcastle Univ, newcastle upon Tyne, United Kingdom; 12Institute of Cellular Medicine, Newcastle Univ, Newcastle upon Tyne, United Kingdom; 13Dept of Med Sciences, Clinical pharmacogenomics and osteoporosis, Uppsala Univ, Uppsala, Sweden
Background: The dose required to achieve a therapeutic INR with warfarin shows inter-individual variability, which is largely dependent on genetic (CYP2C9 and VKORC1) and patient (age and BMI) factors. Study design:This single blind randomized trial was pragmatically designed to determine whether genotype-guided dosing of warfarin was superior to standard dosing. Patients with either atrial fibrillation or venous thromboembolism were randomized into the genotype or standard dosing arms for warfarin treatment, and followed up for 3 months with INR measured at days 0, 4, 6, 8, 15, 22, 57 and 85. The primary outcome measure was time within the target INR range (2.0-3.0) over 3 months. A point-of-care genotyping platform was used to genotype patients for the CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910) and the VKORC1-1639G>A (rs9923231) genotypes, with results being available within 2 hours. The genotype data were used to calculate loading doses for the first 3 days for patients allocated to the genotype arm (using a loading dose algorithm computer software), while the doses on days 4 and 5 were determined according to a dose revision algorithm based on the INR value on day 3. After the initiation period all patients were managed according to routine clinical practice. In the standard dosing arm, patients were given 10mg, 5mg and 5mg daily for the first 3 days respectively (or 5,5,5mg if over >75 years), with subsequent doses being determined by local practice. Results: A total of 455 patients were randomized, with 277 to the genotype-guided dosing arm. At baseline, the two groups were well balanced. The genotype distributions in the genotype arm were similar to those described in the literature. Most patients were males (61%, n=277) with a mean age of 67 years. The majority of patients has AF (72%, n=328). the results of the RCT will be shown in the presentation. Conclusion: The EU-PACT warfarin trial will provide high quality randomized data regarding the utility of genotype-guided warfarin dosing. Novel aspects of the trial include the use of loading and dose revision algorithms, and the point-of-care assay which provided genotyping results in 2 hours.
Author Disclosures: M. Pirmohamed: Research Grant; Significant; EU FP7 framework program. Other Research Support; Significant; UK National Institute for Health Research, UK Medical Research Council, Uk Department of Health. G. Burnside: None. J. Stoddern: None. C. Prince: None. C. Toh: None. T. Nicholson: None. P. Kesteven: None. A. Jorgensen: None. A. Daly: None. A. Maitland-van der Zee: None. P. Williamson: None. N. Eriksson: None. P. Avery: None. F. Kamali: None. M. Wadelius: None.
Key Words: Anticoagulation; Warfarin; Pharmacogenetics; Pharmacogenomics; Atrial fibrillation
The Clarification of Optimal Anticoagulation through Genetics (COAG) Trial
Stephen E Kimmel1, Benjamin French1, Scott E Kasner2, Julie A Johnson3, Jeffrey L Anderson4, Brian F Gage5, Yves D Rosenberg6, Nancy L Geller7, Charles S Eby8, Rosemary Madigan9, Suzanne Goldberg10, Robert D McBane11, Sherif Abdel-Rahman12, Scott M Stevens13, Steven Yale14, Emile R Mohler, III15, Margaret C Fang16, Vinay Shah17, Richard B Horenstein18, Nita A Limdi19, James S Muldowney III20, Patrice Delafontaine21, Jaspal S Gujral22, Robert J Desnick23, Jonathan L Halperin24, Thomas L Ortel25, Henny H Billett26, Robert C Pendleton27, Samuel Z Goldhaber28, Michael D Caldwell29, Robert M Califf30, Jonas Ellenberg1; 1Cntr for Clinical Epidemiology and Biostatistics, Univ PA Sch of Medicine, Philadelphia, PA, 2Hosp of the Univ of Pennsylvania, Univ PA Sch of Medicine, Philadelphia, PA, 3Dept of Pharmacotherapy and Translational Rsch, Univ of Florida, Gainesville, FL, 4Internal Medicine, Univ of Utah Sch of Medicine, Salt Lake City, UT, 5Campus Box 8005, Dept of Medicine, Washington Univ Sch of Medcine, St. Louis, MO, 6National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 7Cntr for Clinical Epidemiology and Biostatistics, National Institutes of Health, Bethesda, MD, 8Dept of Medicine Hematology Div, Washington Univ Sch of Medicine, St. Louis, MO, 9CRCU, Univ PA Sch of Medicine, Philadelphia, PA, 10National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 11Div Internal Medciine and Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, MN, 12Dept of Preventive Medicine & Community Health, Univ of Texas, Galveston, TX, 13Cardiovascular Rsch, Intermountain Med Cntr, Murray, UT, 14Clinical Rsch Cntr, Marshfield Clinical Rsch Foundation, Marshfiled, WI, 15Director of Vascular Medicine, Hosp of the Univ of Pennsylvania, Philadelphia, PA, 16Medicine in Residence, The Univ of California, San Francisco, San Francisco, CA, 17Medicine, Henry Ford Hosp, Detroit, MI, 18Div of Endocrinology Diabetes & Nutrition, Univ of Maryland Sch of Medicine, Baltimore, MD, 19Neurology and Epidemiology, Univ of Alabama at Birmingham, Birmingham, AL, 20Div of Cardiovascular Medicine, Vanderbilt Univ, Nashville, TN, 21Heart and Vascular Institute, Tulane Univ Health Science Cetner, New Orleans, LA, 22Anticoagulation Clnic, Georgia Regents Univ, Augusta, GA, 23Dept of Genetics and Genomic Sciences, Mount Sinai Sch of Medicine, New York, NY, 24Dept of Medicine (Cardiology), Mount Sinai Sch of Medicine, New York, NY, 25Dept of Medicine, Duke Univ Sch of Medicine, Durham, NC, 26Clinical Medicine and Pathology, Montefiore Med Cntr, Bronx, NY, 27Div of General Internal Medicine, Univ of Utah Health Care, Salt Lake City, UT, 28Cardiovascular Div, Brigham and Women's Hosp, Boston, MA, 29General Surgery, Marshfield Clinic, Marshfield, WI, 30Medicine; Div of Cardiology, Duke Univ Med Cntr, Durham, NC
Achieving effective and safe administration of warfarin therapy continues to be a challenge. Although several studies have examined the potential for genetic-based dosing to improve anticoagulation control, research to date has been inconclusive. COAG is the only double-blinded clinical trial to examine the effects of genotype-guided dosing in patients initiating warfarin and is larger than all prior trials combined. COAG is an NHLBI-sponsored, multi-center, double-blind, randomized clinical trial, comparing two approaches to warfarin initiation. Clinical and genotype data were collected on all participants who were then randomized to either a pharmacogenetic algorithm (including clinical factors) or a clinical-only algorithm dosing arm. Each arm received an initial warfarin dose based on the algorithms and then a genetic or clinical revision algorithm on days 4 and/or 5 that included prior doses, clinical variables, and INR values. After the intervention, further dose adjustments were based on INR response, using a standardized dose-titration protocol in both arms. Blinding of warfarin dose was maintained until the primary, 4 week endpoint, at which point participants proceeded to open-dose warfarin and continued to be followed for up to 5 additional months. Primary outcome was the percentage of time in therapeutic range (PTTR) during the first 4 weeks of therapy. Secondary outcomes included the occurrence of INR >4 or serious clinical events, bleeding, and thromboembolism. Analysis was by intention-to-treat, and the study was powered to detect an absolute difference in PTTR of 5% among all patients and 9% among those with a difference in first day algorithm-predicted doses of at least 1 mg/day between the 2 arms. From September, 2009-April, 2013, 1015 adults were enrolled from 18 clinical centers in the US. The mean age (SD) of participants was 57 (16), 51% were male, and 27% African American. The indication for treatment was atrial fibrillation/flutter (22%), DVT/PE (58%), and other/multiple (20%). Final results of primary and secondary endpoints will be presented. Findings from the COAG trial will determine the clinical utility of pharmacogenetics amongst patients who are starting on warfarin therapy.
Author Disclosures: The Disclosure Block has exceeded its maximum limit. Please call Tech support at (217) 398-1792 for more information.
Key Words: Anticoagulants; Pharmacogenetics; Anticoagulation; Genetics
ENGAGE AF-TIMI 48 Primary Results
Robert P Giugliano1, Christian T Ruff1, Eugene Braunwald1, Sabina A Murphy1, Laura T Grip1, Joshua M Betcher2, Shirali P Patel3, Indravadan Patel4, James Hanyok5, Minggao Shi6, Michele Mercuri5, Elliott M Antman1; 1Cardiovascular Medicine, Brigham and Women's Hosp, Boston, MA, 2Biostatistics, Quintiles, Morrisville, NC, 3Project Managment, Quintiles, Durham, NC, 4Cliniical Development, Daiichi-Sankyo, Edison, NJ, 5Clinical Development, Daiichi-Sankyo, Edison, NJ, 6Biostatistics, Daiichi-Sankyo, Edison, NJ
Background: Edoxaban is an investigational, oral, once-daily anticoagulant that specifically and reversibly inhibits factor Xa with rapid onset, linear pharmacokinetics, and half-life of 8-10h. In a phase 2 study of 1146 patients with atrial fibrillation (AF) followed for 3 months, bleeding was dose-related and lower with once-daily compared to twice-daily dosing. Methods:ENGAGE AF-TIMI 48 (NCT00781391) was a randomized, double-blind, placebo-controlled, study of 21,105 subjects with moderate to high risk (CHADS2 ≥2) AF comparing warfarin (target INR 2.0-3.0) to two dosing regimens of edoxaban. At randomization, subjects were stratified based on CHADS2 and edoxaban dose adjustment for drug clearance (based on renal function, use of strong P-gp inhibitors, body weight). Dosing could also be dynamically adjusted throughout the trial. Blinding was maintained through the use of a sham INR algorithm. The primary endpoints were a composite of stroke and systemic embolism (efficacy); and International Society on Thrombosis and Haemostasis (ISTH) major bleeding (safety). Cardiovascular events and overall mortality were also assessed. Results:Baseline characteristics are shown in Table 1. The primary and key secondary endpoints will be available in August 2013 and presented at the meeting. Conclusion:ENGAGE AF-TIMI 48 is the single largest phase 3 trial of a novel anticoagulant in AF and will provide definitive evidence of the efficacy and safety of two dosing regimens of edoxaban compared to well-managed warfarin.
Author Disclosures: R.P. Giugliano: Honoraria; Modest; Daiichi-Sankyo, Merck. Consultant/Advisory Board; Modest; Amgen, Daiichi-Sankyo, Janssen, Lexicon, Merck, Sanofi. Research Grant; Significant; Amgen, Daiichi-Sankyo, Merck. Consultant/Advisory Board; Significant; Beckman-Coulter. C.T. Ruff: Research Grant; Significant; Daiichi-Sankyo. Honoraria; Modest; Daiichi-Sankyo. Consultant/Advisory Board; Modest; Daiichi-Sankyo. E. Braunwald: Research Grant; Significant; Daiichi-Sankyo, Johnson & Johnson. Honoraria; Modest; Daiichi-Sankyo, Bayer. S.A. Murphy: Research Grant; Significant; Daiichi-Sankyo. L.T. Grip: Research Grant; Significant; Daiichi-Sankyo. J.M. Betcher: Research Grant; Significant; Daiichi-Sankyo. S.P. Patel: Research Grant; Significant; Daiichi-Sankyo. I. Patel: Employment; Significant; Daiichi-Sankyo. J. Hanyok: Employment; Significant; Daiichi-Sankyo. M. Shi: Employment; Significant; Daiichi-Sankyo. M. Mercuri: Employment; Significant; Daiich-Sankyo. E.M. Antman: Research Grant; Significant; Daiichi-Sankyo.
Key Words: Factor xa; Atrial fibrillation; Stroke; Anticoagulants; Embolism
Clinical Science: Special Reports: Application of Cell-Based Therapies to Treat Cardiac and Peripheral Diseases
Mechanisms of Bone Marrow Derived Cell Therapy in Ischemic Cardiomyopathy with Left Ventricular Assist Device (LVAD) Bridge to Transplant
April Stempien-Otero1, Deri Helterline1, Tabitha Plummer1, Stephen Farris1, Andrew Prouse2, Eileen Friedman1, Creighton Don1, Nayak Polissar3, Derek Stanford4, Nahush Mokadam5; 1Medicine/Cardiology, Univ of Washington Sch of Med, Seattle, WA, 2Medicine, Univ of Washington Sch of Med, Seattle, WA, 3Biostatistics, Univ of Washington Sch of Med, Seattle, WA, 4Statistics, Mountain-Whisper-Light Statistics, Seattle, WA, 5Surgery, Univ of Washington Sch of Med, Seattle, WA
Clinical trials report small but significant improvements in cardiac function and myocardial blood flow with direct injection of bone marrow cells (BMC) into the hearts of patients with ischemic cardiomyopathy. Pre-clinical data suggest that these cells improve vascular density. To determine the mechanisms by which BMC improve cardiac function we tested the hypothesis that BMC stem cells (CD34+) will improve histologic measurements of vascularity in human subjects undergoing placement of LVAD as a bridge to cardiac transplantation. Methods: Eligible subjects with ischemic cardiomyopathy who were scheduled for placement of an LVAD as a bridge to cardiac transplantation underwent collection of bone marrow the day prior to surgery. Bone marrow was processed in a cGMP facility into three different cell fractions (BMC, CD34+, and CD34-). At the time of LVAD placement the fractions and a saline control were injected from the epicardium into predetermined areas of ischemia and each injection site marked via surgical suture. At the time of transplant injected areas were identified, excised and processed for histology. Data are analyzed by paired t-test comparing the effect of cell fractions injected within the each subject. Results: Six subjects completed the study. There were similar and not statistically significant amounts of bleeding and arrhythmias with the procedure vs nine control subjects. Preliminary histologic analysis of the primary endpoint indicates that myocardium injected with CD34+ stem cells has decreased density of CD31+ endothelial cells in comparison to saline injected myocardium (0.58±0.32 versus 1.1±0.79 percent CD31 positive area ± S.D., P = 0.02 by paired t-test). There were no major differences in fibrosis or inflammation between groups. Analysis of differences in microvascular density and cell proliferation between cell therapies and control injections will be completed for all groups and presented. Conclusions: Tissue analysis in these patients does not support the hypothesis that bone marrow derived CD34+ cells promote increased vascular tissue in humans with ischemic cardiomyopathy via direct injection. We anticipate that further analysis will uncover novel mechanisms by which cell therapy improves cardiac function.
Author Disclosures: A. Stempien-Otero: None. D. Helterline: None. T. Plummer: None. S. Farris: None. A. Prouse: None. E. Friedman: None. C. Don: None. N. Polissar: None. D. Stanford: None. N. Mokadam: None.
Key Words: Heart failure; Stem cell therapy
Assessment of Safety and Efficacy of Autologous Mesenchymal Stem Cells and Whole Bone Marrow in Patients with Ischemic Cardiomyopathy: The TAC-HFT Trial
Joshua M Hare1, Alan W Heldman1, Darcy L DiFede1, Juan P Zambrano2, Joel E Fishman3, Barry H Trachtenberg4, Muzammil Mushtaq1, Adam R Williams1, Ian McNiece5, Jose DaSilva1, Viky Suncion1, Vasileios Karantalis1, John Byrnes6, Maureen H Lowery1, Victor Soto2, Gustavo Lopera7, Roberto Miki1, Howard Willens1, Robert Hendel1, Raul Mitrani1, Eduard Ghersin8, Pradip Pattany8, Gary Feigenbaum9, Behzad Oskouei1, Cheryl Wong Po Foo10, Peter Altman10, Didier Rouy10, Julio Sierra1, Marietsy V Pujol1, Cindy Delgado1, Phillip J Gonzalez11, Jose E Rodriguez1, Erica Anderson12, Adam M Mendizabal12, Richard Schwarz1; 1Interdisciplinary Stem Cell Institute/ Div of Cardiology, Univ of Miami, Miami, FL, 2Div of Cardiology, Jackson Memorial Hosp, Miami, FL, 3Interdisciplinary Stem Cell Institute/Dept of Radiology, Univ of Miami, Miami, FL, 4Dept of Cardiology, Weill Cornell Med College Methodist DeBakey, Houston, TX, 5Dept of Stem Cell Biology, MD Anderson Cancer Cntr, Houston, TX, 6Interdisciplinary Stem Cell Institute/ Hematology/Oncology, Univ of Miami, Miami, FL, 7Div of Cardiology, Miami VA Healthcare System, Miami, FL, 8Interdisciplinary Stem Cell Institute/ Div of Radiology, Univ of Miami, Miami, FL, 9Internal Medicine, Univesity of Southern California, Los Angeles, CA, 10Science and Clinical, BioCardia InC, San Carlos, CA, 11Interdisciplinary Stem Cell Institute/ Div of Stroke, Univ of Miami, Miami, FL, 12Regulatory Divison, EMMES Corp, Rockville, MD
Whole bone marrow (BMCs) and specific bone marrow constituents, such as culture expanded mesenchymal stem cells (MSCs) are both under evaluation in patients with ischemic cardiomyopathy (ICM). The relative feasibility, safety, and efficacy of using these cells to treat patients with ICM remains unknown, and whether specific constituents are superior to BMCs has never been compared in a clinical trial. Accordingly, we conducted TAC-HFT, a randomized, blinded, placebo-controlled comparison of autologous BMCs vs. MSCs vs. placebo. Patients with ICM received 200 million cells or placebo delivered by transendocardial stem cell injection (TESI) in 10 sites at the border zone of left ventricular scar using the Biocardia Helical Infusion Catheter. Of 65 randomized patients, 59 received TESI and were followed for 12 months for safety and efficacy endpoints (LV volumes, regional and global LV function, Minnesota Living with Heart Failure scores (MLH), exercise 6MWT, NYHA class, and peak VO2max). There were no treatment-emergent serious adverse event (TE-SAE) primary endpoints within 30-days, and no deaths or cardiac perforations. Incidence of SAEs by 30-days did not differ: BMCs (n=2 SAEs), MSCs (n=2 SAEs), and respective placebo groups (n=3 SAEs). There were no significant pericardial effusions post-injection. The MLH score improved after both MSC (-11.6; 95% CI, -23.69, 0.49; p=0.006) and BMC (-15.80; 95% CI, -28.63, -2.97; p=0.04) treatment; only MSCs improved the 6-minute walk distance (28.2 meters after 6 months; 95% CI, 10.8-45.5; p=0.005). Myocardial infarct size as a percentage of LV Mass was reduced by MSCs (-18.9%; 95% CI, -30.4 to -7.4; p=0.004) but not BMCs. Regional myocardial function at the site of injection was improved by MSCs but not by BMCs. LV chamber volume and global EF were not changed. Transendocardial stem cell injection (TESI) with autologous MSCs or BMCs was safe in patients with ICM, and MSCs improved myocardial contractility at the site of injection, reduced scar tissue, and enhanced patient functional capacity. These data suggest that culture expanded MSCs have greater biologic activity yet similar safety as BMCs.
Author Disclosures: J.M. Hare: None. A.W. Heldman: None. D.L. DiFede: None. J.P. Zambrano: None. J.E. Fishman: None. B.H. Trachtenberg: None. M. Mushtaq: None. A.R. Williams: None. I. McNiece: None. J. DaSilva: None. V. Suncion: None. V. Karantalis: None. J. Byrnes: None. M.H. Lowery: None. V. Soto: None. G. Lopera: None. R. Miki: None. H. Willens: None. R. Hendel: None. R. Mitrani: None. E. Ghersin: None. P. Pattany: None. G. Feigenbaum: None. B. Oskouei: None. C. Wong Po Foo: None. P. Altman: None. D. Rouy: None. J. Sierra: None. M.V. Pujol: None. C. Delgado: None. P.J. Gonzalez: None. J.E. Rodriguez: None. E. Anderson: None. A.M. Mendizabal: None. R. Schwarz: None.
Key Words: Stem cell therapy; Ischemic heart disease; Magnetic resonance imaging; Heart failure; Cardiomyopathy
Intramyocardial Injection of Allogeneic Mesenchymal Precursor Cells in Left Ventricular Assist Device Patients
Deborah D Ascheim1, Yoshifumi Naka2, Nicholas G Smidera3, Lemuel A Moye4, Sangjin Lee5, Charles T Klodell6, Anita Szady7, Michael K Parides1, Neal Jeffries8, Donna Skerret9, Doris A Taylor10, Kenneth Margulies11, Carmelo Milano12, Joseph G Rogers13, Todd Dewey14, Eric Eichorn14, Benjamin Sun15, David Feldman15, Daniel Goldstein16, Patrick T O'Gara17, Robert D Simari18, Sonia Skarlatos8, Wendy Taddei-Peters8, Marissa Miller8, Emilia Bagiella1, Annetine C Gelijns1, Joseph Y Woo19; 1Health Evidence and Policy, Icahn Sch of Medicine at Mount Sinai, New York, NY, 2Surgery, Columbia Univ Med Cntr, New York, NY, 3Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland, OH, 4Surgery, Univ of Texas Sch of Public Health, Houston, TX, 5Surgery, Cleveland Clinic Foundation, Cleveland, OH, 6Surgery, Univ of Florida, Gainsville, FL, 7medicine, Univ of Florida, Gainsville, FL, 8National Heart Lung and Blood Insititute, National Institutes of Health, Bethesda, MD, 9------, Mesoblast, Ltd., New York, NY, 10Biorepository Rsch, Texas Heart Insititute, Houston, TX, 11Medicine, Hosp of the Univ of Pennsylvania, Philadelphia, PA, 12Sugery, Duke Univ, Durham, NC, 13Surgery, Duke Univ, Durham, NC, 14Surgery, Baylor Healthcare System, Dallas, TX, 15Surgery, Minneapolis Heart Institute, Minneapolis, MN, 16Surgery, Montefiore-Einstein Med Cntr, Bronx, NY, 17Dept of Cardiology, Brigham and Women's Hosp, Boston, MA, 18Medicine, Mayo Clinic, Rochester, MN, 19Surgery, Hosp of the Univ of Pennsylvania, Philadelphia, PA
BACKGROUND: Intramyocardial administration of allogeneic mesenchymal precursor cells (MPC) injected at the time of left ventricular assist device (LVAD) implantation may contribute to myocardial recovery in advanced heart failure (AHF) patients. This trial, conducted by the NIH-sponsored Cardiothoracic Surgical Trials Network (CTSN) and the Cardiovascular Cell Therapy Research Network (CCTRN), assesses the safety and explores the efficacy of intramyocardial allogeneic MPCs (Mesoblast) as an adjunct to LVAD. METHODS: Thirty patients were randomized at 11 sites in this double-blind, sham procedure controlled trial evaluating a single intramyocardial injection of MPCs on safety, functional status, myocardial function, cardiomyocyte regeneration, and neovascularization in patients with AHF, implanted with an LVAD as bridge to cardiac transplantation (BTT) or destination therapy (DT). Patients were randomly assigned (2:1) to 25 million MPCs or medium alone. The primary safety endpoint is the incidence of infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction, and immune sensitization (90 days post randomization). The key efficacy endpoint is functional status and ventricular function, while weaned from LVAD support (90 days post randomization); other secondary endpoints include neurocognition, adverse events, anti-HLA antibody sensitization, cardiomyocyte regeneration, phenotypic and functional analyses, and chemo- and cytokine quantification. All patients are followed until transplant or until 12 months post randomization, whichever comes first. RESULTS: Enrollment was completed in 15 weeks. All patients have met the primary 90 day efficacy endpoint, and investigators remain blinded to all outcomes until the last patient completes 1 yr final assessment in 08/13. CONCLUSION: This trial will provide important information with regard to the safety and efficacy of MPC injection at the time of LVAD implantation.
Author Disclosures: D.D. Ascheim: Consultant/Advisory Board; Modest; BackBeat Medical, Inc, Velomedix. Y. Naka: Consultant/Advisory Board; Modest; Thoratec Co., Transmedics Inc., Medtronics. N.G. Smidera: None. L.A. Moye: None. S. Lee: None. C.T. Klodell: None. A. Szady: None. M.K. Parides: None. N. Jeffries: None. D. Skerret: Employment; Significant; Mesoblast Ltd. Ownership Interest; Significant; Mesoblast Ltd. D.A. Taylor: Ownership Interest; Significant; Miromatrix Medical Inc. K. Margulies: None. C. Milano: None. J.G. Rogers: Consultant/Advisory Board; Significant; Thoratec. T. Dewey: None. E. Eichorn: None. B. Sun: None. D. Feldman: Consultant/Advisory Board; Modest; Thoratec - no personal funds have been received. Monies only for travel and or to the Foundation/Charity, HeartWare- no personal monies have been receive. Monies only for travel and or to the Foundation/Charity, Medtronic- no personal monies have been received. Monies only for traveland or to the Foundation/Charity., XDx- no personal monies have been receive. Monies only for travel and or to the Foundation/Charity. Research Grant; Significant; NIH, Swiss ROTF. D. Goldstein: Honoraria; Modest; Medical Advisory Board, Thoratec Inc., HeartWare, Inc. Consultant/Advisory Board; Modest; Sunshine Heart Inc. P.T. O'Gara: None. R.D. Simari: None. S. Skarlatos: None. W. Taddei-Peters: None. M. Miller: None. E. Bagiella: None. A.C. Gelijns: None. J.Y. Woo: None.
Key Words: Stem cell therapy; Heart failure; Ventricular assist devices; NHLBI
The NHLBI TIME Trial: One-Year Results
Jay H Traverse1, Timothy D Henry1, Carl J Pepine2, James T Willerson3, David X Zhao4, Stephen G Ellis5, Dejian Lai6, Emerson C Perin3, Marc S Penn7, Antonis K Hatzopoulos8, Jeffrey Chambers9, Kenneth W Baran10, Ganesh Raveendran11, Charles Lambert12, Amir Lerman13, Daniel I Simon14, Adrian P Gee15, John R Forder2, Doris A Taylor3, Christopher R Cogle2, Rachel E Olson1, Sonia I Skarlatos16, Sonia I Skarlatos16, Ray F Ebert16, Lemuel A Moye17, Robert D Simari13; 1Rsch, Minneapolis Heart Institute Foundation at Abbott Northwestern Hosp, Minneapolis, MN, 2Rsch, Univ of Florida College of Medicine, Gainesville, FL, 3Rsch, Texas Heart Institute, St. Luke's Episcopal Hosp, Houston, TX, 4Rsch, Vanderbilt Univ Sch of Medicine, Minneapolis, MN, 5Rsch, The Cleveland Clinic Foundation, Cleveland, OH, 6Rsch, Univ of Texas Sch of Public Health, Houston, TX, 7Rsch, Summa Cardiovascular Institute, Rootstown, OH, 8Rsch, Vanderbilt Univ Sch of Medicine, Nashville, TN, 9Rsch, Metro Cardiology, Mercy Hosp, Coon Rapids, MN, 10Rsch, St. Paul Heart Clinic, United Hosp, St Paul, MN, 11Rsch, Lillehei Heart Institute, Univ of Minnesota, Minneapolis, MN, 12Rsch, Patel Rsch Institute, Pepin Heart Hosp, Tampa, FL, 13Rsch, Mayo Clinic College of Medicine, Rochester, MN, 14Rsch, Univ Hosp Case Med Cntr, Cleveland, OH, 15Rsch, Baylor College of Medicine, Houston, TX, 16Rsch, National Heart, Lung and Blood Institute, Bethesda, MD, 17Biostatistics, Univ of Texas - Sch of Public Health, Houston, TX
Background: The TIME Trial was developed by the NHLBI-sponsored Cardiovascular Cell Therapy Research Network (CCTRN) to determine if the timing of cell therapy administration affects the recovery of LV function following a ST-elevation myocardial infarction (STEMI). TIME was a randomized, placebo-controlled trial of 120 patients with anterior STEMI who were randomized to 150 million autologous bone marrow mononuclear cells (BMCs) or placebo with intracoronary delivery performed on Day 3 or Day 7 following reperfusion with PCI and stenting in patients with at least moderate LV dysfunction (LVEF ≤45%). The primary endpoints were changes in global (LVEF) and regional (infarct and border zone) LV function between baseline and 6 months as determined by cardiac MRI. Overall, no benefit of cell therapy was observed at 6 months compared to placebo following cell delivery on Day 3 or Day 7. Methods and Results: A total of 95 patients had an analyzable sequence of MRI data through one year. Overall, there were significant increases in LVEF and regional LV function, and significant decreases in infarct size and LV mass from Day 3 to 6 months and from Day 3 to one year, that was not enhanced by cell therapy. Each randomized group experienced increases in left-ventricular EDVI and ESVI from Day 3 to one year. No deaths or major adverse events occurred between 6-mo and 1-year in either group confirming the ongoing safety of this therapy in the setting of STEMI with moderate LV dysfunction. Conclusion: A significant reduction in infarct size and LV mass occurs during the first six months following STEMI that is not affected by BMC administration. After one year, the initial improvement in LV function remained stable in both groups and is accompanied by a small, on-going increase in LV volumes. No safety concerns were observed in this high-risk STEMI cohort with moderate LV dysfunction. ClinicalTrials.gov Number, NCT00684021
Author Disclosures: J.H. Traverse: None. T.D. Henry: None. C.J. Pepine: Research Grant; Modest; AHA. Consultant/Advisory Board; Modest; NIH, NHLBI, Lilly. Research Grant; Significant; Pfizer, Park-Davis, Brigham & Women's Hospital, Gilead Sciences, Inc, Baxter, AstraZeneca, Cytori, NHLBI, Amorcyte, InfraReDx, NIH, Sanofi-Aventis. J.T. Willerson: None. D.X. Zhao: None. S.G. Ellis: None. D. Lai: None. E.C. Perin: None. M.S. Penn: None. A.K. Hatzopoulos: None. J. Chambers: None. K.W. Baran: None. G. Raveendran: None. C. Lambert: None. A. Lerman: None. D.I. Simon: None. A.P. Gee: None. J.R. Forder: None. D.A. Taylor: None. C.R. Cogle: None. R.E. Olson: None. S.I. Skarlatos: None. S.I. Skarlatos: None. R.F. Ebert: None. L.A. Moye: None. R.D. Simari: None.
Key Words: Stem cell therapy; STEMI; Cardiac MRI; Infarct size
Safety And Efficacy Of Sitagliptin Plus Granulocyte-colony Stimulating Factor In Patients Suffering From Acute Myocardial Infarction - Sitagrami Trial
Wolfgang M Franz1, Hans Theiss2, Christoph Brenner2, Christine Adrion3, Ullrich Grabmaier2, Daniel Theisen4, Alexander Becker5, Franz Ziegler von5, Hae Yong Sohn6, Ulrich Mansmann7, Gerhard Steinbeck8; 1Cardiology & Angiology, Med.Univ.Innsbruck, Innsbruck, Austria; 2Med. I Cardiology, Ludwig Maximilians Univ, Munich, Germany; 3Med Informatics, Ludwig Maximilians Univ, Munich, Germany; 4Radiology, Ludwig Maximilians Univ, Munich, Germany; 5Med I Cardiology, Ludwig Maximilians Univ, Munich, Germany; 6MedI I Cardiology, Ludwig Maximilians Univ, Munich, Germany; 7Cardiology & Angiology, Ludwig Maximilians Univ, Munich, Germany; 8Med I Cardiologyy, Ludwig Maximilians Univ, Munich, Germany
Aims: G-CSF based stem cell mobilization in combination with an inhibition of DPP-IV (Sitagliptin) after acute myocardial infarction (MI) lead to increased homing of bone marrow derived stem cells to the injured myocardium via the SDF1/CXCR4 axis, reduced remodelling, enhanced ejection fraction (EF) and survival. Therefore we initiated a phase III, multi-centre, randomised, double-blind and placebo-controlled efficacy and safety trial hypothesizing an absolute treatment effect of 3.5% of left ventricular EF 6 months after MI applying G-CSF/Sitagliptin (SITAGRAMI trial; EudraCT Number: 2007-003941-34; www.clinicaltrials.gov; Reg.Nr: NCT00650143). Methods and Results: The last of the 174 patients was enrolled in July 2012. All suffered from large MI (mean creatine kinase elevation 3081+ 2106 U/l) undergoing successful percutaneous coronary intervention within 24 hours. After stratified (diabetes y/n; sex) randomisation in a 1:1 ratio, patients were treated with either placebo or G-CSF (10 μg/kg/d)) over a period of 5 days together with an oral dose of 100 mg Sitagliptin daily for 4 weeks. Magnetic resonance imaging (MRI) was performed at screening visit and after 6 months, additional clinical follow-ups were scheduled at 6 weeks and 12 months. In the final analysis (power 80%), the Placebo group showed an absolute mean change in left ventricular EF of 4.6% (SD 7.9%) corresponding to the improvement reported by the REPAIR-AMI study. We will present primary endpoint data assessing the change of left and right ventricular EF by means of MRI from screening to 6 months of follow-up. Secondary endpoints comprised regional cardiac function, cardiac volumes, myocardial perfusion and extent of non-viable myocardium. Furthermore, we assessed peripheral blood CD34, CD34/KDR and CD34/CD26 positive cells, the occurrence of major adverse cardiac events (death, myocardial infarction, CABG, re-intervention), in stent restenosis, and de novo stenosis using angiography. Conclusion: Final results of this first in men clinical trial using pharmacological stem cell mobilization in combination with SDF-1 related enhanced homing of CXCR4+ bone marrow-derived cells in order to induce myocardial regeneration after myocardial infarction will be reported.
Author Disclosures: W.M. Franz: None. H. Theiss: None. C. Brenner: None. C. Adrion: None. U. Grabmaier: None. D. Theisen: None. A. Becker: None. F. Ziegler von: None. H. Sohn: None. U. Mansmann: None. G. Steinbeck: None.
Key Words: Stem cell therapy; Stem/progenitor cells; Myocardial infarction, STEMI; Magnetic resonance imaging; Regenerative medicine stem cells
Effect of Progenitor Cell Mobilization with Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) in Patients with Peripheral Artery Disease and Claudication; GPAD-II: A Phase II Randomized Study
Joseph Poole, Kreton Mavromatis, Jose Binongo, Ali Khan, Qunna Li, Mohamed Khayata, Elizabeth Rocco, Robert Neuman, Alanna Morris, Matthew Topel, Xin Zhang, Charlene Brown, Jonathan Murrow, Matthew Corriere, Stephanie Clement, Salman Sher, Khuram Ashraf, Amr Rashad, Tarek Kabbany, Arshad Ali, John Oshinski, Young Sup Yoon, Edmund Waller, Arshed Ali Quyyumi; Sch of Medicine, Emory Univ, Atlanta, GA
Patients with peripheral arterial disease (PAD) remain symptomatic with intermittent claudication despite therapy. Experimental studies demonstrate improved perfusion in ischemic hind-limb after mobilization of bone marrow progenitor cells (PCs). We hypothesized that therapy with granulocyte macrophage colony-stimulating factor (GM-CSF) will be safe and will improve exercise capacity by mobilizing PCs in patients with symptomatic PAD. Methods: In a Phase II double-blind, placebo-controlled study, 159 patients (aged 64±8 years, 87% male, 37% diabetic) with atherosclerotic PAD and intermittent claudication were randomized (1:1) to received 4 weeks of subcutaneous injections of GM-CSF (Leukine) 500 μg/day thrice-weekly or placebo. The primary outcome was peak treadmill walking time (PWT) at 3 months. Secondary outcomes were PWT at 6 months, changes in circulating PC levels, ankle-brachial index (ABI), Walking Impairment Questionnaire, and 36-item Short-Form-Health-Survey (SF-36) scores. Results: In the intention-to-treat analysis, the primary endpoint comparing the increase in PWT from baseline to 3 months between the GM-CSF (109±21sec) and the placebo (56.2±21sec) groups had a trend toward significance, p=0.08. In the per-protocol analysis, which excluded 4 patients with protocol deviations, PWT increased by 113±20 sec in 3 months in the GM-CSF group and 44±20 in the placebo group (p=0.02), and this increase was maintained at 6 months. GM-CSF mobilized PCs with peak mobilization at 2 weeks. Subjects with a greater increase in circulating PCs (>100%) had a greater increase in PWT compared to those with <100% increase (131±29 vs. 60±17 sec, p=0.04). Compared to placebo, GM-CSF improved the physical functioning subscore of the SF-36 survey at 3 months (p=0.03). There were no significant differences in the ABI or serious adverse event rates between the groups. Conclusion:One month of thrice-weekly therapy with GM-CSF is safe and appears to improve claudication and exercise time in symptomatic patients with PAD, an effect that is sustained for 6 months. The therapeutic effect is greater in those with greater mobilization of bone marrow PCs. Therapy with GM-CSF warrants further study in patients with PAD
Author Disclosures: K. Mavromatis: None. J. Binongo: None. A. Khan: None. Q. Li: None. M. Khayata: None. E. Rocco: None. R. Neuman: None. A. Morris: None. M. Topel: None. X. Zhang: None. C. Brown: None. J. Murrow: None. M. Corriere: None. S. Clement: None. S. Sher: None. K. Ashraf: None. A. Rashad: None. T. Kabbany: None. A. Ali: None. J. Oshinski: None. Y. Yoon: None. E. Waller: None. A. Quyyumi: None.
Key Words: Peripheral arterial disease; Stem cell therapy
Clinical Science: Special Reports: Biomarkers in Populations
Outcome Impact of Coronary Revascularization Strategy - Reclassification With Fractional Flow Reserve (FFR) at time of diagnostic angiography: Insights from a Large French Multicenter FFR Registry (R3F)
Eric Van Belle1, Gilles Rioufol2, christophe Pouillot3, Thomas Cuisset4, Emmanuel Teiger5, Didier Barreau6, Michel Hanssen7, Loic Belle8, Cyril Besnard9, Christophe Bretelle10, Patrick Dupouy11; 1cardiology, Hopital Cardiologique, Lille, France; 2cardiology, Hopital louis pradel, Lyon, France; 3Unité de Cardiologie Diagnostique & Interventionnelle, Clinique sainte Clotidle, Saint Denis de la Réunion, France; 4cardiologie, CHU Timone, Marseille, France; 5cardiology, hopital henri mondor, Creteil, France; 6cardiology, C.H.I.T.S. Hôpital Sainte Musse, Toulon, France; 7cardiologie, centre hospitalier haguenau, Haguenau, France; 8cardiologie, CH d'Annecy, Annecy, France; 9cardiology, Hôpital de la Croix-Rousse, Lyon, France; 10cardiologie, CH Valence, Valence, France; 11cardiology, Hopital privé d'antony, Antony, France
Fractional flow reserve (FFR) is useful in patients preselected for coronary revascularization. There is no large report of its impact on the decision of coronary revascularization on individual patients referred for diagnostic angiography. Methods: The R3F registry investigated 1,075 consecutive patients undergoing diagnostic angiography including an FFR investigation at 20 french centers(Oct. 2008-June 2010). Investigators were asked to define prospectively their revascularization strategy "a priori" based on angiography alone before performing the FFR. The final revascularization strategy, “reclassification” of the strategy by FFR, and 1-year clinical follow-up were prospectivly recorded. Results: 75% of patients were males with a mean age of 65±11 years. They had nonsignificant (< 50% stenosis) angiographic coronary artery diseas (14%), significant (>50%) angiographic 1 vessel (39%), 2 vessel (28%) or 3 vessel disease (19%). The overall MACE (death, MI, revascularization rate at 1 year was 11.6%. The “strategy a priori” based on angiography alone was medical therapy in 55% and revascularization in 45% (PCI=38% and CABG=7%).The final strategy applied according to FFR measurements was medical therapy in 58% and revascularization in 42% (PCI=32% and CABG=10%). However in individual patients, the final strategy based on the results of the FFR was different from the “strategy a priori” in 43% of the cases: This was observed in 33% of “a priori” medical patients, in 56% of “a priori” PCI patients and in 51% of “a priori” CABG patients. Interestingly, in “reclassified” patients who were treated based on the FFR and not on the angiography based “a priori” decision (n=464), the 1-year outcome was as good as in patients in whom the final decision concurred with the decision “a priori” (n=611, MACE= 11.2% vs. 11.9%, p=0.78). Conclusion: This study demonstrates that the use of FFR during diagnostic angiography is associated with reclassification of the revascularization decision in about half of the patients. It further demonstrates that it is safe to pursue a revascularization strategy divergent to that suggested by angiography alone but guided by FFR measurements. These data further support to the concept of "FFR guided” coronary revascularization.
Author Disclosures: E. Van Belle: None. G. Rioufol: None. C. Pouillot: None. T. Cuisset: None. E. Teiger: None. D. Barreau: None. M. Hanssen: None. L. Belle: None. C. Besnard: None. C. Bretelle: None. P. Dupouy: None.
Key Words: Interventional cardiology
Ten-Year Incidence Rates of Major Cardiovascular Events in 697,690 Immigrants to Ontario, Canada, by Ethnic Group and Country of Birth
Jack V Tu1, Anna Chu1, M. R Rezai1, Helen Guo1, Laura C Maclagan1, Peter C Austin1, Gillian L Booth2, Douglas G Manuel3, Maria Chiu1, Dennis T Ko1, Douglas S Lee1, Baiju R Shah4, Linda R Donovan1, Sulan Dai5, David A Alter1; 1Cardiovascular Rsch Program, Inst for Clinical Evaluative Sciences, Toronto, Canada; 2Li Ka Shing Knowledge Institute, St. Michael's Hosp, Toronto, Canada; 3Clinical Epidemiology Program, Ottawa Hosp Rsch Institute, Ottawa, Canada; 4Chronic Disease & Pharmacotherapy Rsch Program, Inst for Clinical Evaluative Sciences, Toronto, Canada; 5Chronic Disease Surveillance and Monitoring Div, Public Health Agency of Canada, Ottawa, Canada
Background: Canada is the developed world’s most ethnically diverse country but the incidence of major cardiovascular disease (CVD) events in immigrants from different ethnic backgrounds and countries of birth is unknown. Methods: We conducted a population-based retrospective cohort study of 697,690 immigrants aged 30 to 74 years from 196 countries of birth with no history of CVD who arrived in Ontario, Canada between 1985 and 1998, using information from the Citizenship and Immigration Canada database linked to eight population-based health databases. We calculated the prevalence of cardiac risk factors, access to health services and ten-year age-standardized incidence rates of major cardiovascular events between January 1, 2000 and December 31, 2009, including a composite outcome consisting of acute myocardial infarction, stroke, heart failure, revascularization or cardiovascular death. These were compared to an age-matched reference cohort of 5,211,911 long-term residents of Ontario. Results: The ten-year incidence rates of major CVD events varied four-fold across the eight ethnic groups studied as shown in Figure 1 with East Asian (e.g., Taiwan, Hong Kong, China) immigrants having the lowest risk and South Asian (e.g., Sri Lanka, Pakistan, India) males and Latin American/South Asian females having the highest risk overall. By country of birth, male immigrants from Guyana, Iraq, Russia and South Asian countries were at highest risk while female immigrants from Guyana, Iraq and South Asian countries were at highest risk. Variation between ethnic groups in the incidence of the composite outcome was most explained by variation in the prevalence of hyperlipidemia (i.e., total/HDL cholesterol ratio). Conclusions: There are striking variations in the incidence rates of CVD events in immigrants to Canada from different ethnic groups. These data can be used to develop health promotion activities aimed at reducing these disparities in CVD outcomes.
Author Disclosures: J.V. Tu: None. A. Chu: None. M.R. Rezai: None. H. Guo: None. L.C. Maclagan: None. P.C. Austin: None. G.L. Booth: None. D.G. Manuel: None. M. Chiu: None. D.T. Ko: None. D.S. Lee: None. B.R. Shah: None. L.R. Donovan: None. S. Dai: None. D.A. Alter: None.
Key Words: Epidemiology; Risk factors; Disparities; Health promotion; Outcomes
China Rural Health Initiative - Primary Care Provider Study: A Large Cluster-Randomized Controlled Trial of High Cardiovascular Risk Management in Rural China
Lijing L Yan1, Weigang Fang2, Elizabeth Delong3, Chen Yao4, Bruce Neal5, Eric D Peterson6, Xiangxian Feng7, Jingpu Shi8, Jianxin Zhang9, Yuhong Zhang10, Ruijuan Zhang11, Zhixin Hao12, Zhifang Li13, Bo Zhou8, Jixin Sun9, Yi Zhao10, Yan Yu11, Cong Li14, Xian Li12, Yining Huang15, Ningling Sun16, Stephen MacMahon17, Yangfeng Wu18; 1Primary Care and Population Health, The George Institute for Global Health at Peking Univ Health Science Cntr, Beijing, China; 2Dept of Preventive Medicine, Feinberg Sch of Medicine, Peking Union Med College Hosp, Beijing, China; 3Primary Care and Population Health Cntr, Duke Univ, Durham, NC, 4Dept of Biostatistics, Peking Univ Clinical Rsch Institute, Beijing, China; 5The George Institute for Global Health, Australia, The George Institute for Global Health, Australia, Sydney, Australia; 6Primary Care and Population Health Cntr, Duke Clinical Rsch Institute, Durham, NC, 7Changzhi Med College, Changzhi Med College, Shanxi, China; 8First Hosp of China Med Univ, First Hosp of China Med Univ, Shenyang, China; 9Hebei Province Cntr for Disease Prevention and Control, Hebei Province Cntr for Disease Prevention and Control, Shijiazhuang, China; 10Ningxia Med Univ, Ningxia Med Univ, Yinchuan, China; 11Xi’an Jiaotong Univ, Xi’an Jiaotong Univ, Xi’an, China; 12Primary Care and Population Health Cntr, The George Institute for Global Health at Peking Univ Health Science Cntr, Beijing, China; 13Changzhi Med College, Changzhi Med College, Changzhi, China; 14Peking Univ Sch of Public Health, Peking Univ Sch of Public Health, Beijing, China; 15Dept of Cardiology, Peking Univ First Hosp, Beijing, China; 16Dept of Cardiology, Peking Univ People’s Hosp, Beijing, China; 17The George Institute for Global Health, The George Institute for Global Health, Sydney, Australia18The George Institute for Global Health at Peking Univ Health Science Cntr, The George Institute for Global Health at Peking Univ Health Science Cntr, Beijing, China
Background: Worldwide, more than 80% of cardiovascular deaths occur in low and middle-income countries where innovative primary care strategies for the management of high-risk individuals are urgently needed. Methods: The China Rural Health Initiative is a cluster randomized controlled trial designed to evaluate the effects of a low-cost, evidence-based intervention package targeting patients at high risk of cardiovascular disease. A total of 120 villages in Northern rural China with high burden of cardiovascular disease were randomized in equal numbers to the intervention program or to usual care. In the intervention villages, primary care providers were trained to identify, treat, follow up and, when appropriate, refer high-risk patients. Providers received periodic feedback on performance and a modest performance-based financial incentive. The impact of the intervention was assessed from independent random samples (with replacement) surveyed at baseline and after 2 years. Since blood pressure-related conditions are the leading causes of premature death and disability in rural China, the primary outcome was defined as village-specific change in mean systolic blood pressure. Secondary outcomes include village-specific changes in the proportions receiving regular (monthly) check-ups, anti-hypertensive medication, and aspirin (where indicated). Results: Over 2 years, primary care providers identified and managed a total of 5,819 high-risk individuals in the 60 intervention villages. The impact of the intervention program will be assessed from random samples comprising 5,050 individuals at baseline and 5,060 individuals at 2 years, including 917 individuals who were randomly selected to participate in both surveys. Data cleaning and analyses are in progress and results will be reported at the meeting. Conclusion: This is the largest-ever cluster randomized trial of a primary care intervention for the management of high cardiovascular disease risk in China. The results will have direct implications for healthcare policy in China and indirect implications for other economically developing countries facing similar health challenges.
Author Disclosures: L.L. Yan: None. W. Fang: None. E. Delong: None. C. Yao: None. B. Neal: None. E.D. Peterson: None. X. Feng: None. J. Shi: None. J. Zhang: None. Y. Zhang: None. R. Zhang: None. Z. Hao: None. Z. Li: None. B. Zhou: None. J. Sun: None. Y. Zhao: None. Y. Yu: None. C. Li: None. X. Li: None. Y. Huang: None. N. Sun: None. S. MacMahon: None. Y. Wu: None.
Key Words: Cardiovascular disease prevention; Disease management; Quality of medical care; Lifestyle
Clinical Science: Special Reports: Novel Approaches to Treating Hypertension and Atherosclerosis
Does Aspirin Intake at Bedtime Decrease Blood Pressure and Morning Peak of Platelet Reactivity?: A Randomized Cross-over Trial
TN Bonten1, JD Snoep1, WJ Assendelft2, JJ Zwaginga3, MV Huisman4, FR Rosendaal1, J Eikenboom4, JG v Bom1; 1Clinical Epidemiology, Leiden Univ Med Cntr, Leiden, Netherlands; 2Primary care, Nijmegen Univ, Nijmegen, Netherlands; 3JJ van Rood Cntr for Clinical Transfusion Rsch, Sanquin Rsch, Sanquin Netherlands, Leiden, Netherlands; 4Thrombosis and Haemostasis, Leiden Univ Med Cntr, Leiden, Netherlands
Background- Aspirin is used for cardiovascular disease (CVD) prevention by millions of patients on a daily basis. Previous studies in hypertensive subjects suggested that aspirin intake at bedtime reduces blood pressure (-7/5mmHg) compared with on awakening. This has never been studied in CVD patients. Moreover, platelet reactivity and CVD incidence is highest during morning hours. Bedtime aspirin intake may attenuate morning platelet reactivity. This clinical trial examined the effect of aspirin intake at bedtime compared with intake on awakening on 24h ambulatory blood pressure measurement (ABPM) and morning platelet reactivity in patients using aspirin for CVD prevention. Methods and Results- This randomized open-label cross-over trial randomized 290 patients to take 100mg aspirin on awakening or at bedtime during two periods of 3 months. At the end of each period ABPM and morning platelet reactivity was measured. The primary analysis population comprised 263 (ABPM) and 133 (platelet reactivity) patients. Aspirin intake at bedtime did not reduce blood pressure compared with intake on awakening (difference systolic/diastolic: -0.1 [95%CI: -1.0; 0.9] / -0.6 [95% CI: -1.2; 0.0] mmHg). Platelet reactivity during morning hours was reduced with bedtime aspirin intake (difference: -22 ARU [95% CI -35; -9]). Conclusions- This study showed that intake of aspirin at bedtime compared with intake on awakening does not reduce blood pressure of patients with CVD. However, bedtime aspirin reduced morning platelet reactivity, which might reduce excess cardiovascular events during high risk morning hours. Clinical Trial Registration- http://clinicaltrials.gov/:NCT01379079.
Author Disclosures: T. Bonten: None. J. Snoep: None. W. Assendelft: None. J. Zwaginga: None. M. Huisman: None. F. Rosendaal: None. J. Eikenboom: None. J.V. Bom: None.
Key Words: Antiplatelet drugs; Cardiovascular disease prevention; Blood pressure; Interventional studies
Daylight: Vitamin D Therapy in Individuals at High Risk of Hypertension
Pankaj Arora1, Frank Harrell2, Erin Carney3, Derek Guanaga3, Myles Wolf4, Marc Sabatine5, Yanna Song2, Joseph Y Russell3, Courtney Karol3, Michael Torre3, Susan Cheng5, Amanda Zaleski6, Gregory Panza6, Atum Azzahir7, Semerit M Strachan8, Robert Jones9, Sarah Jones9, Adam Reinstein9, Dillon C O'Neill10, Heather Swales6, Gregory Plotnikoff9, Jeffery Dusek9, Christopher Newton-Cheh3, Thomas J Wang10; 1Cardiology Div, Univ of Alabama at Birmingham, Birmingham, AL, 2Biostatistics, Vanderbilt Univ, Nashville, TN, 3Cardiology Div, Massachusetts General Hosp, Boston, MA, 4Div of Nephrology and Hypertension, Univ of Miami Miller Sch of Medicine, Miami, FL, 5Cardiology Div, Brigham and Women's Hosp, Boston, MA, 6Cardiology Div, Hartford Hosp, Hartford, CT, 7Cardiology Div, Cultural Wellness Cntr, Minneapolis, MN, 8Integrative Health Rsch Cntr, Cultural Wellness Cntr, Minneapolis, MN, 9Integrative Health Rsch Cntr, Abbott Northwestern Hosp, Minneapolis, MN, 10Cardiology Div, Vanderbilt Univ, Nashville, TN
Background: In experimental studies, vitamin D deficiency promotes hypertension via enhanced activation of the renin-angiotensin system. While numerous epidemiologic studies have reported an inverse association between vitamin D levels and blood pressure, it is unclear whether vitamin D supplementation benefits blood pressure management. Thus, we hypothesized that vitamin D supplementation would decrease blood pressure in individuals with both vitamin D deficiency and elevated blood pressure. Study design and endpoints Inclusion criteria were 25-OH vitamin D ≤ 25 ng/ml and either pre-hypertension or stage 1 hypertension. We excluded individuals with a history of renal, liver, or cardiovascular disease, use of vitamin D supplements, or use of anti-hypertensive therapy. We enrolled 534 individuals (Table 1) across 4 sites. All subjects were randomized in double-blind fashion to low (400 IU/day) versus high (4000 IU/day) doses of oral vitamin D3 for 6 months. The last follow-up visit will be completed on September 13, 2013. The primary endpoint of the study is mean 24-hour ambulatory systolic blood pressure. Secondary endpoints include 24-hour ambulatory diastolic blood pressure, daytime and nighttime ambulatory blood pressure, and clinic blood pressure. After accounting for dropouts, we estimate that we will have 80% power to detect a 2.8 mm Hg difference in the change in 24-hour mean systolic blood pressure. Conclusion: DAYLIGHT is the first adequately-powered, prospective randomized trial of vitamin D supplementation for elevated blood pressure. Because vitamin D deficiency is common and easy to treat, positive results could suggest a simple and cost-effective option for preventing or treating hypertension in the general population.
Author Disclosures: P. Arora: None. F. Harrell: None. E. Carney: None. D. Guanaga: None. M. Wolf: None. M. Sabatine: None. Y. Song: None. J.Y. Russell: None. C. Karol: None. M. Torre: None. S. Cheng: None. A. Zaleski: None. G. Panza: None. A. Azzahir: None. S.M. Strachan: None. R. Jones: None. S. Jones: None. A. Reinstein: None. D.C. O'Neill: None. H. Swales: None. G. Plotnikoff: None. J. Dusek: None. C. Newton-Cheh: None. T.J. Wang: Research Grant; Modest; DiaSorin Inc. Consultant/Advisory Board; Modest; DiaSorin Inc. Other; Modest; SAB.
Key Words: Blood pressure; Vitamins; Hypertension; Clinical trials; Population science
Effect of Angiotensin II Type I Receptor Blockade on Carotid Artery Atherosclerosis: A Randomized Trial Comparing Valsartan and Placebo (EFFERVESCENT)
Ronnie Ramadan1, Ayman Khoder1, Saurabh Dhawan1, Jose N Binongo2, Asad Ghafoor1, Hamid Syed1, Muhammad Ali1, Charles B Kitchen1, Salman Sher1, Dean Jones1, John Oshinski3, Arshed Ali Quyyumi1; 1Cardiology, Emory Univ, Atlanta, GA, 2Biostatistics, Emory Univ, Atlanta, GA, 3Radiology, Emory Univ, Atlanta, GA
Background: Angiotensin II plays a key role in the pathogenesis of atherosclerosis by increasing oxidative stress (OS). We investigated the effects of Angiotensin II type 1 (AT1) receptor blockade with Valsartan on carotid wall thickness (WT) and atherosclerosis, with the hypothesis that Valsartan will reduce OS and progression of atherosclerosis. Methods: Subjects (n= 120, 60±9 years, 51% male, 83% white, 39% HTN, 7% T2DM) with carotid intima-media thickness >0.65 mm by ultrasound were randomized (2:1) in a double-blind manner to receive either Valsartan (n=80), titrated up to 320mg daily, or placebo (n=40) for 2 years. Subjects on open label statin therapy (n=60) were stratified 2:1 to valsartan or placebo. Bilateral T2-weighted black-blood carotid MRI was performed at baseline, 1 and 2 years. Changes in the carotid bulb vessel wall area, maximum WT, and lumen area were measured. Plaque was defined as >2mm segmental WT of the carotid bulb (n= 86). Systemic OS was estimated by quantification of the major intra- and extra-cellular plasma aminothiols, with the intermediary product cysteineglutathione disulfide (CySSG) serving as an overall measure of OS. Comparison between groups was by linear mixed-effects models, adjusting for multiple measures. Results: The mean vessel wall area decreased after 2 years of Valsartan therapy (-6.7±2.4 mm2; P= 0.008) but remained unchanged with placebo (+3.4±3.1 mm2, P= 0.28), a difference that was significant (P= 0.01) between the groups, and was independent of statin therapy or change in lumen size. Similarly, maximal WT increased with placebo (+0.87±0.21 mm, P<0.001) but remained unchanged with Valsartan (-0.08±0.16 mm; P= 0.61), p<0.001 between groups. Importantly, plaque thickness increased with placebo (+0.73±0.25 mm, P= 0.006) and remained unchanged with Valsartan (-0.23±0.17; P= 0.22), p<0.001 between groups. Finally, CySSG levels increased with placebo to a greater extent compared to Valsartan (+1.8±1.8 μM vs. +0.70±1.1 μM), P= 0.007. Conclusions: AT1 receptor blockade with Valsartan is associated with significant carotid arterial remodeling manifested as regression in WT and lack of progression of atherosclerotic plaque, which was independent of statin use and accompanied by improvements in oxidative stress.
Author Disclosures: R. Ramadan: None. A. Khoder: None. S. Dhawan: None. J.N. Binongo: None. A. Ghafoor: None. H. Syed: None. M. Ali: None. C.B. Kitchen: None. S. Sher: None. D. Jones: None. J. Oshinski: None. A. Quyyumi: None.
Key Words: Angiotensin II; Carotid arteries; Plaque; Drugs
Randomized Comparison of the Safety, Tolerability, and Efficacy of Long-term Administration of AMG 145 versus Standard of Care in 1104 Patients: 52-week Results from the OSLER Study
Michael J Koren1, Robert P Giugliano2, Frederick Raal3, David Sullivan4, Michael Bolognese5, Gisle Langslet6, Fernando Civeira7, Rob Scott8, Ransi Somaratne8, Patric Nelson8, Thomas Liu9, Scott M Wasserman8, Marc S Sabatine2; 1not applicable, Jacksonville Cntr for Clinical Rsch, Jacksonville, FL, 2TIMI Study Group/Cardiovascular Div, Brigham and Women's Hosp, Boston, MA, 3Dept of Medicine, Univ of the Witwatersrand Med Sch, Johannesburg, South Africa; 4Dept of Clinical Biochemistry, Royal Prince Alfred Hosp, Camperdown, Australia; 5not applicable, Bethesda Health Rsch Cntr, Bethesda, MD, 6Lipid Clinic, Oslo Univ Hosp, Oslo, Norway; 7Lipid Clinic, Hosp Universitario Miguel Servet, Zaragoza, Spain; 8Global Development, Amgen Inc., Thousand Oaks, CA, 9Biostatistics, Amgen Inc., Thousand Oaks, CA
Purpose: AMG 145, a monoclonal antibody against PCSK9, significantly reduced LDL-C in phase 2 studies of 12-weeks duration. The open label OSLER study aimed to define the long-term efficacy and safety of PCSK9 inhibition. Methods: Eligible OSLER participants completed any of the four AMG 145 phase 2 studies (MENDEL - monotherapy; LAPLACE-TIMI 57 - on background statin therapy; GAUSS - statin intolerance; or RUTHERFORD - familial hypercholesterolemia). Subjects were randomized 2:1, without consideration of their phase 2 study assignment, to receive subcutaneous AMG 145 420 mg monthly with standard of care (SOC) or SOC alone for 1 year. After 12 weeks, lipid results were prospectively unblended and investigators allowed to adjust SOC therapies. Objectives were to characterize the safety and tolerability of AMG 145 and percent change from phase 2 baseline of various lipid parameters. Results: 1104 (mean age 56±12 [SD] years, 55% female) subjects enrolled in OSLER (81% of those eligible), most (~88%) within 3 days of their last phase 2 visits. 92% of AMG 145+SOC patients and 89% of the SOC group completed 52 weeks of follow-up. Compared to phase 2 baseline LDL-C levels, patients who first received AMG 145 in OSLER experienced a 52.3% reduction in LDL-C (P<0.0001). Patients who received AMG 145 in a parent study and continued AMG 145 plus SOC in OSLER maintained LDL-C reduction (from 50.4% at parent study end to 52.1% at OSLER completion, P<0.0001 vs baseline). Patients who discontinued AMG 145 upon OSLER entry had LDL-C levels revert nearly to baseline by 12 weeks (from 49.5% to 4.3% reductions). Adverse events (AEs) and serious AEs occurred in 73% and 6.3% of SOC patients and in 81% and 7.2% of AMG 145+SOC patients, respectively. Conclusions: Monthly AMG 145 dosing demonstrated sustained efficacy and encouraging safety and tolerability during prolonged treatment of a diverse population of hyperlipidemic patients.
Author Disclosures: M.J. Koren: Research Grant; Modest; Amgen. Other Research Support; Modest; Regeneron, Sanofi, Roche, Pfizer. R.P. Giugliano: Honoraria; Modest; Daiichi-Sankyo, Merck. Consultant/Advisory Board; Modest; Amgen, Daiichi-Sankyo, Janssen, Lexicon, Merck, Sanofi. Research Grant; Significant; Amgen, Daiichi-Sankyo, Merck. Consultant/Advisory Board; Significant; Beckman-Coulter. F. Raal: Other Research Support; Modest; Reimbursement for conducting clinical trials with novel lipid-lowering therapies–Amgen, Sanofi. Speakers Bureau; Modest; AstraZeneca, Pfizer, Merck, Amgen. Honoraria; Modest; AstraZeneca, Pfizer, Merck, Amgen, Sanofi. Consultant/Advisory Board; Modest; AstraZeneca, Pfizer, Merck. D. Sullivan: Research Grant; Significant; AMG studies paid to re-imburse SLHD. Other Research Support; Significant; Other studies for Eli-Lilly, Amaryn, MSD paid to re-imburse SLHD. Honoraria; Modest; MSD, Abbott. Consultant/Advisory Board; Modest; MSD, Amgen, Abbott. M. Bolognese: Research Grant; Significant; X. G. Langslet: Consultant/Advisory Board; Modest; Janssen Pharmaceutical. F. Civeira: Consultant/Advisory Board; Modest; X. R. Scott: Employment; Significant; Amgen Inc. Ownership Interest; Modest; Amgen Inc. R. Somaratne: Employment; Significant; Amgen Inc. Ownership Interest; Modest; Amgen Inc. P. Nelson: Employment; Significant; Amgen Inc. Ownership Interest; Modest; Amgen Inc. T. Liu: Employment; Significant; Amgen Inc. Ownership Interest; Modest; Amgen Inc. S.M. Wasserman: Employment; Significant; Amgen Inc. Ownership Interest; Modest; Amgen Inc. M.S. Sabatine: Research Grant; Modest; Amgen, AstraZeneca, AstraZeneca/Bristol-Myers Squibb Alliance, Bristol-Myers Squibb/Sanofi-aventis Joint Venture, Daiichi-Sankyo, Eisai, Genzyme, GlaxoSmithKline, Merck, Sanofi-aventis, Takeda, Abbott. Consultant/Advisory Board; Modest; Aegerion, Amgen, Diasorin, GlaxoSmithKline, Merck, Pfizer, Sanofi-aventis, AstraZeneca, Vertex. Other; Modest; Research grant (continued): Accumetrics, Critical Diagnostics, Nanosphere, Roche Diagnostics.
Key Words: Hyperlipidemia; Clinical trials; Monoclonal antibodies; Outcomes; Transesophageal echocardiography
Clinical Science: Special Reports: Advanced Cardiovascular Disease: Complications and Challenges
Dedicated ICD Programming Reduces the Number of Inappropriate Therapies in a Real World Primary Prevention ICD Population: The DECREASE - Trial
Joerg Schwab1, Hendrik Bonnemeier2, Christel Bodden3, Frank Birkenhauer3, Frank Eberhardt4; 1Medicine - Cardiology, Univ of Bonn, Bonn, Germany; 2Klinik für Kardiologie und Angiologie, Univ of Schleswig-Holstein, Campus Keil, Kiel, Germany; 3SJM, St. Jude Med GmbH, Eschborn, Germany; 4Kardiologie, Ev. Kliniken Köln, Köln, Germany
Background: A significant number of patients with an implantable cardioverter/defibrillator (ICD) for primary prevention receive inappropriate shocks. Previous studies which have reported a reduction of inappropriate therapies with a simple modification of ICD detection settings excluded patients with single-chamber devices and atrial fibrillation (AF). Our aim was to investigate the effect of raising the ICD detection zone in the entire primary prevention ICD population. Methods: 543 patients receiving an ICD for primary prevention were randomized to either conventional or progressive ICD programming. The detection rate was programmed at 171/min for ventricular tachycardia (VT) and 214/min for ventricular fibrillation (VF) in the Conventional group and 187/min for VT and 240/min for VF in the Progressive group. 43% of patients received single-chamber and 57% dual chamber detection devices. The primary endpoint was freedom from inappropriate therapies and from untreated VT/VF. Results: The primary endpoint was reached in 35 patients (13%) in the Conventional group and 17 patients (6%) in the Progressive group (p=0.004). Progressive ICD programming led to significantly fewer ICD therapies (26% vs. 14%; p<0.001) and shocks (15 % versus 9%; p=0.023) compared to conventional ICD programming. Sub-analyses showed the greatest reduction of inappropriate therapies and shocks in dual-chamber detection devices with progressive compared to single-chamber detection devices with conventional ICD programming (p<0.001). Conclusions: Progressive ICD programming reduces the number of inappropriate therapies and shocks in a broad primary prevention ICD population particularly in combination with dual chamber detection devices.
Author Disclosures: J. Schwab: None. H. Bonnemeier: None. C. Bodden: Employment; Significant; Employee. F. Birkenhauer: Employment; Significant; Employee. F. Eberhardt: None.
Key Words: Implantable cardioconvert defibrillator; Ventricular arrhythmia
A Multicenter, Randomized Study Assessing the Efficacy of Left Ventricular Augmentation with Algisyl-LVR in the Treatment of Advanced Heart Failure Patients with Ischemic and Non-ischemic Cardiomyopathy: Interim Results of the AUGMENT-HF Study
Douglas L Mann1, Hani N Sabbah2, Andy Hinson3, Stefan D Anker4, Andrew Coats5, Randall J Lee6, Gabriel Cristian7, Dinu Dragomir8, Enrico Pusineri9, Ottavio Alfieri10, Antonello Gavazzi11, Benno Rensing12, Maurizio Volterrani13, Anthony Dart14, Luca Bettari15; 1Cardiovascular Div, Washington Univ. Sch of Med, Barnes Jewish Hosp, St. Louis, MO, 2Director of Cardiovascular Rsch, Henry Ford Health System, Detroit, MI, 3Clinical & Regulatory Affairs, LoneStar Heart Inc, Laguna Hills, CA, 4Dept of Cardiology, Charité, Campus Virchow-Klinikum, Berlin, Germany; 5Cardiology, Monash Univ, Australia, UK, Melbourne, Australia; 6Div of Cardiology Electrophysiology Service, UCSF, San Francisco, CA, 7Cardiology, Military Hosp Bucharest, Bucharest, Romania; 8Cardiology, Spitalul Clinic De Urgenta MAI, Bucharest, Romania; 9Cardiology, IRCCS San Donato, San Donato Milanese, Italy; 10Cardiac Surgery, Ospedale San Raffaele, Milan, Italy; 11Cardiology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy; 12Cardiology, St. Antonius Ziekenhuis, Nieuwegein, Netherlands; 13Dip. Cardiologia, IRCCS San Raffaele Pisana, Rome, Italy; 14Heart Failure/ Transplant Cardiology, The Alfred Hosp, Melbourne, Australia; 15Cardiology, Istituti Ospitalieri di Cremona, Cremona, Italy
Introduction: Therapeutic options for patients with HF, refractory to pharmacological and device therapies are limited. Reduction of LV wall stress is considered a cornerstone in the treatment of HF. Algisyl-LVR is a proprietary biopolymer gel injected into the LV free wall as a permanent implant. Prior preclinical and clinical studies of Algisyl-LVR demonstrated attenuation of LV remodeling and improvements in LV function. Hypothesis: Treatment with Algisyl LVR is superior to standard medical therapy in the management of advanced chronic HF secondary to ischemic or non-ischemic dilated cardiomyopathy (DCM). Methods: AUGMENT-HF is a multi-center, prospective, randomized, evaluation of Algisyl-LVR in patients with ischemic or non-ischemic DCM. This pre-specified interim analysis of 29 patients randomized 1 to 1 (14 Algisyl-LVR;15 Controls). Patients, mean age 63.3±9.1, symptomatic HF with Peak VO2 of 12.24±1.17 ml/min/kg, LVEF of 25.34±4.71% and LVEDDi of 30 to 40mm/m2 (LVEDD/BSA). Patients were on stable, evidence-based HF therapy. Study endpoints include measures of functional capacity (CPX, 6-MWT, and NYHA class) and cardiac function (echo and MRI). Results: Algisyl-LVR implants (n=14) were successfully performed with no device-related complications. There was no 30-day mortality or significant arrhythmia observed in the Algisyl-LVR group. At 3 months, the Algisyl-LVR group had a significant improvement in 6-MWT distance from 234.4±66.8m at baseline to 327.6±96.6m (p=0.014), whereas patients in control group had a decline in 6-MWT at 3 months (304.5±76.4m at baseline; 294.6±96.2m at 3 months; p = 0.773). There was a highly significant improvement of NYHA class with Algisyl-LVR (3.13±0.35 at baseline to 2.27±0.47 after 3 months, p<.00001); while the control group had a non significant decrease in NYHA class (2.93±0.59 at baseline to 2.75±0.62 at 3 months; p=0.446). Blinded core lab evaluations of CPX, Echo and MRI will be presented with KCCQ and PGA QOL scores. Conclusions: The interim clinical study observations support the novel concept that LV augmentation with Algisyl-LVR in the failing heart can be performed safely in patients with advanced HF, and may be lead to functional improvement in health status in these patients with advanced HF.
Author Disclosures: D.L. Mann: Consultant/Advisory Board; Modest; Scientific Advisory Board. H.N. Sabbah: Consultant/Advisory Board; Significant; Scientific Advisory Board. A. Hinson: Employment; Significant; Employee of LoneStar Heart Inc. S.D. Anker: Consultant/Advisory Board; Significant; Scientific Advisory Board. A. Coats: Consultant/Advisory Board; Significant; Scientific Advisory Board. R.J. Lee: Consultant/Advisory Board; Modest; Scientific Advisory Board. G. Cristian: None. D. Dragomir: None. E. Pusineri: None. O. Alfieri: None. A. Gavazzi: None. B. Rensing: None. M. Volterrani: None. A. Dart: None. L. Bettari: Consultant/Advisory Board; Modest; Medical Advisor.
Key Words: Heart failure; Cardiomyopathy; Infarction; Stress; Exercise tests
Session XIV: Late-Breaking Abstracts in Resuscitation Science
A Multicenter Randomized Trial Comparing a Mechanical CPR Algorithm Using LUCAS Versus Manual CPR in Out-of-Hospital Cardiac Arrest Patients–Per Protocol Analysis of the LINC Study
Sten Rubertsson1, Erik Lindgren1, Ollie östlund1, Johan Herlitz2, Rolf Karlsten1; 1Uppsala Univ, Uppsala, Sweden; 2Borås Univ, Borås, Sweden
Background: Disruption in manual chest compressions due to fatigue resulting in incorrect compression rate and depth as well as pauses for defibrillation might be major factors contributing to poor outcome after out-of-hospital cardiac arrest (OHCA). We hypothesized that mechanical chest compressions using the LUCAS device and defibrillation during ongoing chest compressions (L-CPR) would improve 4-hr survival as compared to guideline-based manual cardiopulmonary resuscitation (M-CPR) in OHCA. Method: In 6 European sites, January 2008 to August 2012, 2589 patients with OHCA were randomized to either L-CPR or M-CPR. 219 patients were excluded from the Per protocol Population due to violation of inclusion/exclusion criteria, treatment cross over or missing 4-hr survival data resulting in n=1172 in the L-CPR and n=1198 in the M-CPR group. Surviving patients were evaluated for neurological outcome using the Cerebral Performance Category (CPC) score with CPC 1-2 classified as good outcome. Results: There was no difference in background variables between the groups. The survival rate at 4-hr was 279 patients (23.8%) with L-CPR and 281 (23.5%) with M-CPR (risk difference 0.35%, 95% C.I. -3.07 - 3.77, p=0.85). Survival with good neurological outcome was 101 (8.6%) vs 92 (7.7%) (p=0.41) at hospital discharge, 99 (8.5%) vs 88 (7.4%) (p=0.36) at one month and 104 (8.9%) vs 90 (7.6%) (p=0.26) at 6 months after CA in the L-CPR and M-CPR group respectively. The proportion of survivors with CPC1-2 in the L-CPR and M-CPR group were 92% vs 85% at hospital discharge, 93% vs 87% at one month and 99% vs 94% at 6 months after arrest. Conclusions: There was no difference in short or long-term survival up to 6 months between patients treated with the LUCAS concept as compared to manual CPR in the Per protocol Population. There was good neurological outcome in the vast majority of survivors in both groups.
Author Disclosures: S. Rubertsson: Research Grant; Modest; PI for the LINC study. Consultant/Advisory Board; Modest; Physio-Control/Jolife AB. E. Lindgren: None. O. Östlund: None. J. Herlitz: None. R. Karlsten: None.
Key Words: Cardiac arrest; Cardiopulmonary resuscitation; Outcomes
Is Participation in Get With The Guidelines–Resuscitation Associated with Improved Quality of Cardiac Arrest Care?
Monique L Anderson1, Graham Nichol2, David Dai1, Paul S Chan3, Sana M Al-Khatib1, Steven M Bradley4, Eric D Peterson1; 1Duke Univ, Durham, NC, 2Univ of Washington, Seattle, WA, 3St. Luke's Mid-Atlantic Heart Institute, Kansas City, MO, 4Univ of Colorado, Denver, CO
Introduction: There is large variation in care and outcome after cardiac arrest. Certain processes of care are associated with improved outcome after in-hospital cardiac arrest (IHCA). We determined if duration of hospital participation in Get With the Guidelines- Resuscitation (GWTG-R) quality improvement program was associated with improved care. Methods: Adherence to six recommended processes of care and a composite quality measure was assessed in patients with IHCA. Composite adherence was defined as proportion of correct care out of total care opportunities. A patient level analysis adjusted for patient and hospital factors, as well as calendar year, in multivariable regression models to assess the association between duration of participation in GWTG-R and composite adherence. Results: Included were 124,058 patients from 449 hospitals from 2000 to 2010. Median age was 69 years (IQR 58-78); 58% were male and 66% were white. 19.0% had ventricular fibrillation (VF) or tachycardia (VT) From baseline to the 10th year, participating hospitals improved most quality measures: confirmation of endotracheal tube (29.6% change), monitored/witnessed event (7.1%), time to first compressions < 1 min (1.4%), time to vasopressor 2 min after previous shock (27.6%), and the overall composite score (9.8%) [P<0.001 for comparisons] (See Figure 1). Time to first shock < 2 min did not significantly change over time. Time in GWTG-R was independently associated with improved composite score (OR 1.15 per year, 95% 1.14-1.17). Conclusions: Participation in a resuscitation quality improvement program improves quality of care over time. Time to first defibrillation shock for VF/VT patients has not improved.
This research has received full or partial funding support from the American Heart Association.
Author Disclosures: M.L. Anderson: None. G. Nichol: Research Grant; Modest; Philips Healthcare Inc, Velomedix Inc. D. Dai: None. P.S. Chan: Research Grant; Modest; AHA, NHLBI. S.M. Al-Khatib: None. S.M. Bradley: None. E.D. Peterson: Research Grant; Significant; AHA.
Key Words: Cardiac arrest; Quality of medical care; Performance measurement
Post-discharge Outcomes After Resuscitation from Out-of-Hospital Cardiac Arrest: A ROC PRIMED Substudy
Graham Nichol1, Danielle Guffey2, Ian G Stiell3, Brian Leroux2, Sheldon Cheskes4, Ahamed Idris5, Peter J Kudenchuk6, Rene MacPhee7, Lynn Wittwer8, Jon Rittenberger9, Thomas D Rea6, Kellie Sheehan2, Valerie Rac10, Keitki Raina9, Kyle Gorman11, Tom Aufderheide12, Resuscitation Outcomes Consortium Investigators; 1Univ of Washington - Harborview Cntr for Prehospital Emergency Care and Clinical Trial Cntr, Univ of Washington, Seattle, WA, 2Clinical Trial Cntr, Univ of Washington, Seattle, WA, 3Ottawa Health Rsch Institute, Ottawa, Canada; 4Sunnybrook Cntr for Prehospital Medicine Regions of Halton and Peel, Toronto, Canada; 5Univ of Texas Southwestern, Dallas, TX, 6King County EMS, Seattle and King County Public Health, Seattle, WA, 7Wilfred Laurier Univ, Waterloo, Canada; 8Clark Regional Emergency Services Authority, Emergency Med Services Program, Vancouver, WA, 9Univ of Pittsburgh Med Cntr, Univ of Pittsburgh, Pittsburgh, PA, 10Univ of Toronto, Toronto, Canada; 11Clackamas Fire District #1, Clackamas, OR, 12Med College of Wisconsin, Milwaukee, WI
IMPORTANCE Assessment of morbidity is an important component of evaluating interventions for or the adequacy of resuscitation of patients with out-of-hospital cardiac arrest (OHCA). OBJECTIVE We evaluated among survivors of OHCA cognition, functional status, health-related quality of life (HRQL) and depression as functions of patient and emergency medical services (EMS) factors; compared those with complete vs. missing post-discharge measures; and correlated outcomes after OHCA. DESIGN Prospective cohort sub study of a randomized trial. SETTING The parent trial studied two comparisons in persons with non-traumatic OHCA treated by EMS personnel participating in the Resuscitation Outcomes Consortium. The first randomly allocated persons to undergo cardiopulmonary resuscitation with an active or sham impedance threshold device (ITD). The second randomly allocated clusters of individuals with OHCA to early or late rhythm analysis. PARTICIPANTS Consenting patients who survived to discharge. MAIN OUTCOME MEASURES Post-discharge telephone assessments included neurologic function (modified Rankin score, MRS), cognitive impairment (Adult Lifestyle and Function Mini Mental Status Examination, ALFI-MMSE), HRQL (Health Utilities Index Mark 3, HUI3) and depression (Telephone Geriatric Depression Scale, T-GDS). RESULTS 729 (56% of survivors) consented. 644 (88% of consented) completed > 1 assessment. Likelihood of assessment was associated with baseline characteristics and study site. Most survivors had MRS ≤= 3 (82.7%), no cognitive impairment (82.7% ALFI-MMSE ≥= 17), no severe impairment in health (71.6%, HUI3 ≥0.7) and no depression (90.1% T-GDS ≤= 10). Post-discharge outcomes did not differ between trial intervention or over time. CONCLUSIONS Most respondents had no, mild or moderate impairment in health. Concern about poor quality of life is not a valid reason to abandon efforts to resuscitate an individual or to improve an EMS system’s response to cardiac arrest.
Author Disclosures: G. Nichol: Research Grant; Significant; Resuscitation Outcomes Consortium (NIH U01 HL077863-06). D. Guffey: Research Grant; Modest; Resuscitation Outcomes Consortium (NIH U01 HL077863-06). I.G. Stiell: Research Grant; Modest; Resuscitation Outcomes Consortium (NIH U01 HL077863-06). B. Leroux: Research Grant; Modest; Resuscitation Outcomes Consortium (NIH U01 HL077863-06). S. Cheskes: Research Grant; Modest; Resuscitation Outcomes Consortium (NIH U01 HL077863-06). A. Idris: Research Grant; Modest; Resuscitation Outcomes Consortium (NIH U01 HL077863-06). P.J. Kudenchuk: Research Grant; Modest; Resuscitation Outcomes Consortium (NIH U01 HL077863-06). R. MacPhee: Research Grant; Modest; Resuscitation Outcomes Consortium (NIH U01 HL077863-06). L. Wittwer: Research Grant; Modest; Resuscitation Outcomes Consortium (NIH U01 HL077863-06). J. Rittenberger: Research Grant; Modest; Resuscitation Outcomes Consortium (NIH U01 HL077863-06). T.D. Rea: Research Grant; Modest; Resuscitation Outcomes Consortium (NIH U01 HL077863-06). K. Sheehan: Research Grant; Modest; Resuscitation Outcomes Consortium (NIH U01 HL077863-06). V. Rac: Research Grant; Modest; Resuscitation Outcomes Consortium (NIH U01 HL077863-06). K. Raina: Research Grant; Modest; Resuscitation Outcomes Consortium (NIH U01 HL077863-06). K. Gorman: Research Grant; Modest; Resuscitation Outcomes Consortium (NIH U01 HL077863-06). T. Aufderheide: Research Grant; Modest; Resuscitation Outcomes Consortium (NIH U01 HL077863-06).
Key Words: Cardiac arrest; Interventional studies; Outcomes
Therapeutic Hypothermia for the Treatment of Acute Myocardial Infarction – The CHILL-MI Trial
David Erlinge1, Matthias Götberg1, Irene Lang2, Michael Holzer3, Marco Noc4, Peter Clemmensen5, Ulf Jensen6, Bernhard Metzler7, Stefan James1, Hans Erik Botker8, Elmir Omerovic9, Jan Harnek1, Marcus Carlsson10, Henrik Engblom10, Hakan Arheden10, Lars Wallentin11, Göran K Olivecrona1; 1Dept of Cardiology, Lund, Sweden; 2Dept. of Cardiology, AKH, Vienna, Austria; 3AKH, Emergency Medicine, Vienna, Austria; 4Dept of Cardiology, Ljuliana, Slovenia; 5Dept of Cardiology, Copenhagen, Denmark; 6Dept of Cardiology, Karolinska, Stockholm, Sweden; 7Dept of Cardiology, Innsbruck, Austria; 8Dept of Cardiology, Aarhus, Denmark; 9Dept of Cardiology, Gothenburg, Sweden; 10Dept of Clinical Physiology, Lund, Sweden; 11Dept of Cardiology, Uppsala, Sweden
BACKGROUND: Previous clinical studies of hypothermia in awake patients with ST-elevation myocardial infarction (STEMI) failed to reduce infarct size. However, therapeutic temperature (≤35°C) was usually not reached prior to coronary reperfusion. A feasibility study of rapid combination cooling before reperfusion (RAPID MI-ICE), significantly reduced infarct size. We aimed to confirm this finding in a larger prospective, randomized, multicentre, efficacy trial (The CHILL-MI trial). METHODS: 120 patients in nine centers in Sweden, Austria, Denmark and Slovenia with large STEMI’s with a duration of <6 hours, planned to undergo primary PCI were randomised to hypothermia induced by rapid infusion of 600-2000 ml cold saline combined with endovascular cooling or standard of care. The primary endpoint was myocardial infarct size as a percentage of myocardium at risk, assessed by cardiac magnetic resonance imaging (MRI) at 4±2 days. RESULTS: Time from onset of symptom to randomisation was 119 (86-165) vs. 120 (90-150) minutes (median (Q1-Q3), control vs. hypothermia). Hypothermia was initated before PCI and continued for 1 h after reperfusion toward a target temperature of 33°C followed by spontaneous rewarming. Patients randomised to hypothermia treatment achieved a mean core body temperature of 34.7°C before reperfusion. Door-to-balloon time was 9 min longer in the hypothermia group. At 45±15 days there was no mortality and no increase in the incidence of heart failure in the hypothermia group. The 45 days results will have been presented. The 6 month results (second MRI for infarct size and clinical events) will be presented at RESS AHA 2013. DISCUSSION: The study demonstrates the feasibility of cooling STEMI patients to a core body temperature of ≤35°C before reperfusion, with an acceptable delay of primary PCI. The lack of a difference in early mortality is indicative of the safety of the used treatment algorithm. The CHILL-MI trial will provide evidence on whether hypothermia during primary PCI reduces infarct size up to 6 months. (ClinicalTrials.gov id NCT01379261).
Author Disclosures: D. Erlinge: Speakers Bureau; Modest; Philips. M. Götberg: None. I. Lang: None. M. Holzer: None. M. Noc: None. P. Clemmensen: None. U. Jensen: None. B. Metzler: None. S. James: None. H. Botker: None. E. Omerovic: None. J. Harnek: None. M. Carlsson: None. H. Engblom: None. H. Arheden: None. L. Wallentin: None. G.K. Olivecrona: None.
Key Words: STEMI; Hypothermia
Randomised Comparison of the Effectiveness of the Laryngeal Mask Airway Supreme, i-gel and Current Practice in the Initial Airway Management of Out-of-Hospital Cardiac Arrest (REVIVE-Airways): Clinical Outcomes
Jonathan R Benger1, David Coates2, Sian E Davies3, Rosemary Greenwood4, Megan Rhys2, Matthew Thomas4, Sarah Voss1, Jerry P Nolan5; 1Univ of the West of England, Bristol, Bristol, United Kingdom; 2South Western Ambulance Service NHS Foundation Trust, Exeter, United Kingdom; 3Univ of Bristol, Bristol, United Kingdom; 4Univ Hosps Bristol NHS Foundation Trust, Bristol, United Kingdom; 5Royal United Hosp Bath NHS Trust, Bath, United Kingdom
Introduction: The optimal approach to airway management during out of hospital cardiac arrest (OHCA) is unknown, and evidence from observational studies is conflicting. Methods: We completed a randomised trial comparing two second generation supraglottic airway devices (the i-gel and laryngeal mask airway supreme (LMAS)) to usual practice (determined by the attending paramedic, but principally tracheal intubation) during OHCA. 171 paramedics from an ambulance service in Southwest England were randomised to one of the three arms and used their allocated method of initial airway management for every OHCA patient attended between March 2012 and February 2013. Patients were followed up for 90 days. Results: From a total of 2990 OHCA, 1375 (46%) underwent active resuscitation. Of these, 711 (57%) were attended by a participating paramedic. 96 were excluded according to pre-specified criteria; 615 patients were enrolled (232 i-gel, 174 LMAS, 209 usual practice) with 100% follow-up. The LMAS arm was suspended after 10 months due to staff safety concerns. The baseline characteristics of the three groups were similar. The rates of transport to hospital, return of spontaneous circulation and admission did not differ (p=0.28, p=0.91 and p=0.58 respectively). Survival to discharge was: i-gel 10.3%, LMAS 8.0%, usual practice 9.1% (p=0.73) and to 90 days was: i-gel 9.5%, LMAS 6.9%, usual practice 8.6% (p=0.65). Neurocognitive function and quality of life at 90 days also showed no difference. Overall, tracheal intubation was attempted in 46% (267/584), and was successful on the first attempt in 85%. The i-gel was superior to the LMAS in compliance, adverse events, the need to change airway device (29% i-gel vs. 39% LMAS: p=0.053) and staff feedback. Conclusions: We found no significant differences in important clinical outcomes between the use of a supraglottic airway device and usual practice (principally tracheal intubation) during OHCA, but the trial was insufficiently powered to detect small differences in mortality. The i-gel was superior to the LMAS on several measures. We are proceeding to a large-scale randomised trial of the i-gel versus tracheal intubation in OHCA.
Author Disclosures: J.R. Benger: None. D. Coates: None. S.E. Davies: None. R. Greenwood: None. M. Rhys: None. M. Thomas: None. S. Voss: None. J.P. Nolan: None.
Key Words: Cardiac arrest; Ventilation
Session VIII: Best Original Resuscitation Science Poster Session and Reception
Evaluation of the Relationship of Functional Survival with the Three-phase Model of Out-Of-Hospital Cardiac Arrest in the Era of Targeted Temperature Management
Ian R Drennan1, Kevin E Thorpe2, Laurie J Morrison3; 1Rescu, Keenan Res Ctr, Li Ka Shing Knowledge Inst, St Michael's Hosp; Inst of Med Sciences, Faculty of Med, Univ of Toronto, Toronto, Canada; 2Dalla Lana Sch of Public Health, Univ of Toronto; Applied Health Rsch Ctr, St. Michael's Hosp, Toronto, Canada; 3Rescu, Keenan Res Ctr, Li Ka Shing Knowledge Inst, St Michael's Hosp; Inst of Med Sciences, Faculty of Med, Univ of Toronto; Div of Emergency Medicine, Dept of Medicine, Univ of Toronto, Toronto, Canada
Background: Patient survival from out-of-hospital cardiac arrest (OHCA) decreases from the time of collapse to initial shock. This decrease in survival has been shown to occur in relation to the 3-phase model of cardiac arrest physiology: electrical, circulatory and metabolic. There is limited research evaluating the relationship of the 3-phase model to functional survival at hospital discharge. Furthermore the effect of targeted temperature management (TTM) on functional survival during each phase is unknown. Objective: This study aims to determine the effect of TTM on the relationship between the time of first shock and functional survival at hospital discharge. Furthermore, it will examine the effect of TTM on functional survival during each of the three phases of cardiac arrest physiology. Methods: This was a retrospective observational study of consecutive OHCA patients with initial shockable rhythm, treated by EMS personnel. Included patients obtained a return of spontaneous circulation (ROSC) in-hospital and were eligible for TTM. Multivariable logistic regression was used to determine the effect of time of initial shock on functional survival (Modified Rankin Scale) at discharge between patients who underwent TTM and those that did not. Results: There were 19,065 adult OHCA of presumed cardiac etiology treated by EMS, 871 were eligible for TTM. Of these patients 622 (71.4%) survived to hospital discharge, 487 (55.9%) with good neurological outcome. Poor functional survival at hospital discharge was associated with older age (OR 0.32; 95% CI 0.24-0.42), and longer time from collapse to initial shock (OR 0.32; 95% CI 0.22-0.46), while TTM was associated with improved functional survival (OR 1.63; 95% CI 1.07-2.46). Functional survival decreased during each phase of the model (73.1% vs. 68.4% vs. 52.7%, p<0.001). There was a significant interaction between TTM and the time to initial shock on functional survival (p<01). Conclusion: Functional survival at hospital discharge was associated with the length of time to initial shock, and decreased during each phase of the 3-phase model of cardiac arrest physiology. Post-arrest TTM was associated with improved functional survival and the effect of TTM was dependent upon the time of initial shock.
Author Disclosures: I.R. Drennan: None. K.E. Thorpe: None. L.J. Morrison: None.
Key Words: Resuscitation; Cardiac arrest; Outcomes
Different Characteristics of Chronic Heart Failure due to Pump Failure and Bradyarrythmia
Mai Iwataki1, Yun-Jeong Kim2, Byung-Joo Sun2, Jeong-Yoon Jang2, Masaaki Takeuchi1, Hiroshi Kuwaki1, Kyoko Otani1, Nobuhiko Haruki1, Hidetoshi Yoshitani1, Robert A. Levine3, Jae-Kwan Song2, Yutaka Otsuji1; 1Univ of Occupational and Environmental Health, Kitakyushu City, Japan; 2Asan Med Ctr, Seoul, Korea, Republic of; 3Massachusetts General Hosp, Boston, MA
Background: Chronic heart failure (CHF) can be caused by both left ventricular (LV) pump failure as well as bradyarrythmias without LV pump failure. Hemodynamic differences between CHF by LV pump failure and bradyarrythmia have not been fully investigated. We hypothesized that CHF by LV pump failure can be associated with both reduced cardiac output and increased lung congestion due to associated LV diastolic dysfunction while CHF by bradyarrythmia can be associated with reduced cardiac output but only mild lung congestion due to the absence of LV diastolic dysfunction. Methods and Results: Subjects consists of 39 patients with CHF due to LV pump failure (LV ejection function < 35% without other cardiac structural disease), 24 patients with CHF due to bradyarrythmia and 18 normal subjects. Compared to patients with CHF by LV pump failure, those with CHF by bradyarrythmia had significantly lower heart rate, less dilated LV, preserved LV ejection fraction, preserved or even augmented stroke volume, similarly reduced cardiac index, less dilated laft atrium, preserved E/E’, and less increased BNP or NT pro BNP. Conclusions: CHF by LV pump failure is characterized with both significantly reduced cardiac output and lung congestion while CHF by bradyarrythmia is characterized with similarly reduced cardiac output but only modest lung congestion.
Author Disclosures: M. Iwataki: None. Y. Kim: None. B. Sun: None. J. Jang: None. M. Takeuchi: None. H. Kuwaki: None. K. Otani: None. N. Haruki: None. H. Yoshitani: None. R. Levine: None. J. Song: None. Y. Otsuji: None.
Key Words: Echocardiography
Nifekalant Versus Amiodarone in the Treatment of Cardiac Arrest: An Experimental Study in a Swine Model of Prolonged Ventricular Fibrillation
George Karlis1, Nicoletta Iacovidou2, Pavlos Lelovas3, Panagiota Niforopoulou2, Apostolos Papalois4, Ioanna Siafaka2, Theodoros Xanthos2; 1Sismanoglio General Hosp, Athens, Greece; 2Univ of Athens, Athens, Greece; 3Biomedical Rsch Foundation of the Academy of Athens, Athens, Greece; 4Experimental-Rsch Cntr ELPEN Pharmaceutical, Athens, Greece
Introduction: The purpose of the experiment was to compare the effects of nifekalant and amiodarone on return of spontaneous circulation (ROSC), survival, as well as on hemodynamic parameters in a swine model of prolonged ventricular fibrillation (VF). Hypothesis: We hypothesized that the antiarrhythmic agent nifekalant, due to its unique pure potassium channel blocking properties, is superior to amiodarone, in terms of ROSC and short-term survival, in the treatment of cardiac arrest. Methods: After 8 min of untreated VF arrest, bolus doses were administered of adrenaline (0.02 mg/kg) and either nifekalant (2 mg/kg), or amiodarone (5 mg/kg), or saline (n = 10 per group) after randomization. Cardiopulmonary resuscitation (CPR) was commenced immediately after drug administration and defibrillation was attempted 2 min later. CPR was resumed for another 2 min after each defibrillation attempt and the same dose of adrenaline was given every 4th minute during CPR. Hemodynamic monitoring and mechanical ventilation continued for 6 h after return of spontaneous circulation (ROSC) and the pigs were euthanized at 48 h. Researchers were blinded for drug groups throughout the study. Results: 48-h survival rate was significantly higher with nifekalant compared to amiodarone (p=0.0005) and saline (p=0.02), (9/10 vs. 0/10 vs. 3/10, respectively), while there was no difference in the rate of ROSC between the three treatment groups (p=0.082). Systolic aortic pressure, diastolic aortic pressure and coronary perfusion pressure were significantly higher with nifekalant during CPR and immediate post-resuscitation period (p<0.05). The animals in amiodarone group had a slower heart rate at the 1st and 45th min post-ROSC (p<0.0005 and p=0.006, respectively). The number of electric shocks required for terminating VF, time to ROSC and adrenaline dose were significantly higher with amiodarone compared to nifekalant (p=0.0005). There was no difference in the incidence of post-resuscitation ventricular tachycardia (VT) between the groups (p=0.091). Conclusions: Nifekalant showed a more favorable hemodynamic profile and improved survival compared to amiodarone and saline in this swine model. It may represent a promising antiarrhythmic drug for the treatment of VF/VT.
Author Disclosures: G. Karlis: None. N. Iacovidou: None. P. Lelovas: None. P. Niforopoulou: None. A. Papalois: None. I. Siafaka: None. T. Xanthos: None.
Key Words: Amiodarone; Ventricular fibrillation; Resuscitation
Bridging The Gap - Prehospital Video Analysis of an Autopulse Extrication System to Enable Quality Resuscitation Whilst Moving Out-of-hospital Cardiac Arrest Patients
Richard M Lyon1, Colin Crookston2, Anna Crawford1, Gareth R Clegg1, Resuscitation Rsch Group Edinburgh; 1Univ of Edinburgh, Edinburgh, United Kingdom; 2Scottish Ambulance Service, Edinburgh, United Kingdom
Background:Refractory OHCA may require treatment, e.g. rescue PCI, that cannot be delivered prehospital. Moving patients during OHCA is deleterious because manual CPR is not practical whilst carrying a patient from the scene of their arrest to the transporting vehicle. In a moving vehicle manual CPR is difficult to execute effectively, and hazardous to rescuers. Aim:To assess whether an Autopulse and carry-sheet can maintain CPR, bridging from prehospital to in-hospital. Methods:Firstly, we measured CPR in 52 cases over a 12 month period 26-August-2011 to 24-August-2012 in Edinburgh. Locally, extrication using a scoop-stretcher requires stopping CPR and disconnecting the defibrillator until the patient is in the ambulance. QCPR data from Philips MRX defibrillators revealed the time taken to extricate patients by measuring the disconnection period. Since April 2010, a specialist second tier Resuscitation Rapid Response Unit (3RU) has responded to OHCA in Edinburgh. In the second phase of our project from August 2011, we used an Autopulse and carry-sheet for extrication. The 3RU paramedics wore a video camera (VideoBadge, Edesix, UK) allowing later analysis. Results:During manual resuscitation, extrication resulted in a continuous break for a median time of 276s (54s-846s, n=52). During Autopulse/carry-sheet deployment the median time without any CPR was 42s (15s - 100s, n=58). The Autopulse system achieved uninterrupted, effective CPR whilst moving patients down stairs and around difficult corners. The flexibility afforded by the carry-sheet made transporting large patients down narrow staircases much more straightforward than with the scoop stretcher. Also, median extrication times using the carry-sheet were shorter than when using the scoop 155s (46s-726s, n=35) vs 276s (54s-846s)(P<0.001). Conclusion:Video recording demonstrates the impact of equipment change on resuscitation quality. The Autopulse/carry-sheet system allows maintenance of high quality CPR during extrication and transport. There is minimal interruption in CPR during deployment and rapidity of extrication is increased. Further research is warranted to assess the clinical impact of early transport of OHCA patients for in-hospital intervention.
Author Disclosures: R.M. Lyon: Consultant/Advisory Board; Modest; Prometheus Medical Ltd, Physio Control. Other; Modest; Medical equipment from Zoll Medical. C. Crookston: None. A. Crawford: None. G.R. Clegg: None.
Key Words: Cardiopulmonary resuscitation; Resuscitation
Team Performance in Resuscitation During In-Hospital Mock Codes
Charles N Pozner1, Ashley Barash2, Seth P Jones2, Steven Yule1; 1Harvard Med Sch, Boston, MA, 2Neil and Elise Wallace STRATUS Cntr for Med Simulation, Brigham & Women’s Hosp, Boston, MA
Introduction Of the more than 200,000 patients who suffer cardiac arrest in hospitals annually in the United States, only 21% recover sufficiently to return home. Early and effective resuscitation by code teams is vital to survival. By surreptitiously placing a medium-fidelity patient simulator in the hospital and calling for help from clinicians, we recreate many aspects of the code event. This study uses observation to measure performance of local responders and code teams, comparing key metrics (time to defibrillate) against national standards. Method We analyzed 89 mock codes from 2004-2012 in inpatient (n=43), outpatient (n=14), procedural (n=19) and nonclinical (n=13) areas of the hospital. Materials: A clinician educator and simulation specialist transported a full-body simulator (Laerdal MegaCode Kelly with Vital Sim/SimPad, Stavengar, Norway) to a random location in the hospital. Procedure: The simulator was set in ventricular fibrillation. A bystander was alerted and told that they must manage the simulator as they would a real patient; including providing care (C-A-B, defibrillation, IV, Airway management, medication administration), calling for local help and/or paging the code team. Participants were unaware that the code was simulated until arrival. Up to 25 people were involved in each event. The case ended when sinus rhythm was achieved after one or two defibrillations at 200 Joules. Measurement: The primary endpoint was time to defibrillation after alerting the bystander. Results The overall mean time from alert to defibrillation was 384 seconds (SD=177). Only 7.8% of the codes met the national standard of defibrillation within 180 seconds. Performance was best in inpatient areas (14% defibrillated within 180 seconds). Conclusion We found that most codes did not meet national guidelines for time to defibrillate. It is possible that the guidelines are clinically appropriate but unrealistic to consistently achieve in practice. Our unique reality-driven approach studies clinical teams responding to what they believe to be a real emergency. Simulation used in this way provides insight into hospital systems and helps process improvement.
Author Disclosures: C.N. Pozner: None. A. Barash: None. S.P. Jones: None. S. Yule: None.
Key Words: Resuscitation; Healthcare innovation; Quality assessment
Physical Shortfalls in CPR Quality and Methods for Quality Improvement
Robert H Trenkamp, Jr., Fernando J Perez; Saving Lives In Chatham County, Savannah, GA
INTRODUCTION The distribution of various chest stiffness of cardiac arrest victims can be estimated from published data. Measurements were made on fifty subjects. Performance in various compression modalities was calculated. The 2010 guidelines have doubled the force required for compliance, and the force required to compress 90% of victims’ chests to 2005 guideline depth will compress about 40% to the 2010 guideline. MATERIAL AND METHODS Test subject data was gathered in person and with an online questionnaire. The data collected were total body weight and “hands on scale weight” - the reading of a scale when performing manual chest compression on the scale with enough force to cause the knees to slightly leave the floor. Other data were collected to support the search for a proxy for “hands on scale weight.” The “hands on scale weight“ was used as a proxy for the maximum value of the body weight component of total force and in calculating deceleration force. This overstates maximum manual compression capacity but assures a more uniform collection of that component. The viscosity force was neglected due to its limited contribution. A similar calculation was made for pedal compressions using total body weight. Anonymity of the test subject and the subject’s organization were preserved. This was a condition of participation by most subjects. The percentage of victim chests on which each subject could perform two-inch compressions was calculated for manual and pedal compressions, both with and without weighted vests. FINDINGS Pedal compressions eliminated 42% of the gap between capability and guidelines. Weight vests had a similar, additive effect. CONCLUSION Bystanders should be taught the pedal compression technique. It provides increased endurance and increases the percentage of of chests on which they can perform two-inch compressions. Weighted vests offer an increase in capability to healthcare workers and should be used in hospital and pre-hospital settings when a chest too stiff to compress is encountered. The applicability of the pedal compression mode for pre-hospital personnel needs to be studied.
Author Disclosures: R.H. Trenkamp: None. F.J. Perez: None.
Key Words: Cardiac arrest; Cardiopulmonary resuscitation; Guidelines
- © 2013 American Heart Association, Inc.
- Late-Breaking Clinical Trials: Acute Cardiovascular and Cerebrovascular Care
- Late-Breaking Clinical Trials: Prevention: From Schools to Countries
- Late-Breaking Clinical Trials: Medical and Surgical Approaches to Improving Heart Failure Outcomes
- Late-Breaking Clinical Trials: Therapeutic Advances in Coronary and Peripheral Vascular Disease
- Clinical Science: Special Reports: Biomarkers in Populations
- Clinical Science: Special Reports: Novel Approaches to Treating Hypertension and Atherosclerosis
- Clinical Science: Special Reports: Advanced Cardiovascular Disease: Complications and Challenges
- Session XIV: Late-Breaking Abstracts in Resuscitation Science
- Session VIII: Best Original Resuscitation Science Poster Session and Reception
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