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EDITOR IN CHIEF ASSOCIATE EDITORS William C. Roberts, MD Vincent E. Friedewald Baylor Heart & Vascular Institute Paul A. Grayburn Baylor University Medical Center ASSISTANT EDITORS Wadley Tower No. 457 3600 Gaston Avenue Robert C. Kowal Dallas, Texas 75246 Jeffrey M. Schussler (214)826-8252 Fax: (214)826-2855 EDITORIAL BOARD CARDIOVASCULAR Rodney H. Falk Joseph Lindsay, Jr. Robert J. Siegel MEDICINE John A. Farmer Gregory Y.H. Lip Marc A. Silver In Adults David P. Faxon Francisco Lopez-Jimenez Ross J. Simpson, Jr. Ted Feldman Joseph Loscalzo Steven N. Singh Antonio Abbate Jack Ferlinz G.B. John Mancini Burton E. Sobel J. Dawn Abbott Jerome L. Fleg Francis E. Marchlinski John C. Somberg George S. Abela Gerald F. Fletcher Frank I. Marcus Jamil Aboulhosn David H. Spodick Joseph A. Franciosa Barry J. Maron Joseph S. Alpert Lynne W. Stevenson Gary S. Francis Martin S. Maron Martin A. Alpert Gregory W. Stone W. Bruce Fye Randolph P. Martin Ezra A. Amsterdam John R. Stratton William H. Gaasch Attilo Maseri Jeffrey L. Anderson Jonathan M. Tobis Julius M. Gardin Charles Maynard Evan Appelbaum Eric J. Topol Bernard J. Gersh Michael D. McGoon Richard W. Asinger Byron F. Vandenberg S. David Gertz Darren K. McGuire Pablo Avanzas Hector O. Ventura Mihai Gheorghiade Raymond G. McKay Gary John Balady D. Luke Glancy Jawahar L. Mehta George W. Vetrovec Eric Bates Stephen P. Glasser Bernard Meier Robert A. Vogel Jeroen J. Bax Michael R. Gold Franz H. Messerli Ron Waksman George A. Beller Samuel Z. Goldhaber Eric L. Michelson David D. Waters William E. Boden Robert E. Goldstein Richard V. Milani Nanette K. Wenger Monty M. Bodenheimer Sidney Goldstein Alan B. Miller Robert Wilensky Robert O. Bonow Steven A. Goldstein Wayne L. Miller James T. Willerson Jeffrey S. Borer J. Anthony Gomes Gary S. Mintz Clyde W. Yancy Martial G. Bourassa Antonio M. Gotto, Jr. Fred Morady Barry L. Zaret Eugene Braunwald K. Lance Gould Lori Mosca Douglas P. Zipes Jeffrey A. Brinker Donald C. Harrison Arthur J. Moss David L. Brown Philip D. Henry James E. Muller In Infants and Children Michael E. Cain L. David Hillis Gerald B. Naccarelli Hugh D. Allen Richard O. Cannon III David R. Holmes, Jr. Navin C. Nanda Bruce S. Alpert Bernard R. Chaitman Mun K. Hong Robert A. O’Rourke Stanley J. Goldberg Kanu Chatterjee William G. Hundley Erik Magnus Ohman Warren G. Guntheroth John S. Child Ami S. Iskandrian Richard L. Page Howard P. Gutgesell Robert J. Cody Allan S. Jaffe Sebastian T. Palmeri John D. Kugler Lawrence S. Cohen Hani Jneid Seung-Yung Park James E. Lock Marc Cohen Greg L. Kaluza Eugene R. Passamani John W. Moore C. Richard Conti Joel S. Karliner Alan S. Pearlman Lowell W. Perry Michael H. Crawford John A. Kastor Carl J. Pepine David J. Sahn James P. Daubert Sanjiv Kaul Joseph K. Perloff Richard M. Schieken Gregory J. Dehmer Ellen C. Keeley Bertram Pitt James A. de Lemos Kenneth M. Kent Philip J. Podrid CARDIOVASCULAR SURGERY Anthony N. DeMaria Richard E. Kerber Don Poldermans Eugene H. Blackstone Pablo Denes Dean J. Kereiakes Arshed A. Quyyumi Lawrence I. Bonchek George A. Diamond Morton J. Kern Charles E. Rackley Lawrence H. Cohn John P. DiMarco Spencer B. King III C. Venkata Ram John A. Elefteriades Allen Dollar Robert E. Kleiger Nathaniel Reichek Hartzel V. Schaff Michael J. Domanski George J. Klein Robert Roberts RELATED SPECIALISTS Gerald Dorros Lloyd W. Klein Jennifer G. Robinson L. Maximilian Buja Uri Elkayam Paul Kligfield Lynda E. Rosenfeld Kenneth A. Ellenbogen Robert A. Kloner Melvin M. Scheinman Jean-Pierre Despres Myrvin H. Ellestad John B. Kostis David J. Schneider Michael Emmett Stephen G. Ellis Charles Landau John S. Schroeder Giovanni Filardo Toby R. Engel Richard L. Lange Patrick Washington Serruys Barry A. Franklin Andrew E. Epstein Carl J. Lavie Pravin M. Shah Charles B. Higgins N. A. Mark Estes, III Carl V. Leier Prediman K. Shah Jeffrey E. Saffitz Michael Ezekowitz B. T. Liang Jamshid Shirani Renu Virmani A5 THE AMERICAN JOURNAL OF CARDIOLOGY姞 CONTENTS VOL. 107, NO. 4 FEBRUARY 15, 2011 Coronary Artery Disease Comparison of Morbidity and Mortality in Diabetics Versus Nondiabetics Having Isolated Coronary An Early and Simple Predictor of Severe Left Main Bypass Versus Coronary Bypass plus Valve and/or Three-Vessel Disease in Patients With Operations Versus Isolated Valve Operations ....535 Non–ST-Segment Elevation Acute Coronary Serenella Castelvecchio, Lorenzo Menicanti, Syndrome ......................................................495 Ekaterina Baryshnikova, Carlo de Vincentiis, Masami Kosuge, Toshiaki Ebina, Kiyoshi Hibi, Alessandro Frigiola, and Marco Ranucci, for the Satoshi Morita, Mitsuaki Endo, Nobuhiki Maejima, Surgical and Clinical Outcome Research (SCORE) Noriaki Iwahashi, Kozo Okada, Toshiyuki Ishikawa, Group Satoshi Umemura, and Kazuo Kimura Reperfusion by Primary Percutaneous Coronary Heart Failure Intervention in Patients With ST-Segment Elevation Relation of Bundle Branch Block to Long-Term Myocardial Infarction Within 12 to 24 Hours of the (Four-Year) Mortality in Hospitalized Patients With Onset of Symptoms (from a Prospective National Systolic Heart Failure ......................................540 Observational Study [PL-ACS]) .........................501 Alon Barsheshet, Ilan Goldenberg, Moshe Garty, Marek Gierlotka, Mariusz Gasior, Krzysztof Wilczek, Shmuel Gottlieb, Amir Sandach, Michal Hawranek, Janusz Szkodzinski, Piotr Paczek, Avishag Laish-Farkash, Michael Eldar, and Andrzej Lekston, Zbigniew Kalarus, Marian Zembala, Michael Glikson and Lech Polonski Review Characteristics of Depression Remission and Its Relation With Cardiovascular Outcome Among Percutaneous Coronary Intervention for Non Patients With Chronic Heart Failure (from the ST-Elevation Acute Coronary Syndromes: Which, SADHART-CHF Study) ......................................545 When and How? ............................................509 Wei Jiang, Ranga Krishnan, Maragatha Kuchibhatla, Robert K. Riezebos, Jan G.P. Tijssen, Michael S. Cuffe, Carolyn Martsberger, Freek W.A. Verheugt, and Gerrit J. Laarman Rebekka M. Arias, and Christopher M. O’Connor, for the SADHART-CHF Investigators Coronary Artery Disease Long-Term Follow-Up of Patients With First-Time Warfarin Use and Outcomes in Patients With Chest Pain Having 64-Slice Computed Advanced Chronic Systolic Heart Failure Without Tomography ...................................................516 Atrial Fibrillation, Prior Thromboembolic Events, or Fabiola B. Sozzi, Filippo Civaia, Philippe Rossi, Prosthetic Valves .............................................552 Jean-Francois Robillon, Stephane Rusek, Marjan Mujib, Abu-Ahmed Z. Rahman, Ravi V. Desai, Frederic Berthier, Francois Bourlon, Laura Iacuzio, Mustafa I. Ahmed, Margaret A. Feller, Gilles Dreyfus, and Vincent Dor Inmaculada Aban, Thomas E. Love, Michel White, Usefulness of Cooling and Coronary Catheterization Prakash Deedwania, Wilbert S. Aronow, to Improve Survival in Out-of-Hospital Cardiac Gregg Fonarow, and Ali Ahmed Arrest ............................................................522 Dion Stub, Christopher Hengel, William Chan, Editorial Damon Jackson, Karen Sanders, Anthony M. Dart, Andrew Hilton, Vincent Pellegrino, James A. Shaw, The Risk of Thromboembolism in Heart Failure: Stephen J. Duffy, Stephen Bernard, and David M. Kaye Does It Merit Anticoagulation Therapy? ............558 Eduard Shantsila and Gregory Y.H. Lip Two-Year Safety and Effectiveness of Sirolimus- Eluting Stents (from a Prospective Registry) .......528 Heart Failure Bimmer E. Claessen, Roxana Mehran, Martin B. Leon, Eric A. Heller, Giora Weisz, George Syros, Trials on the Effect of Cardiac Resynchronization on Gary S. Mintz, Theresa Franklin-Bond, Arterial Blood Pressure in Patients With Heart Irene Apostolidou, Jose P.S. Henriques, Failure ...........................................................561 Gregg W. Stone, Jeffrey W. Moses, and Sameer Ather, Sripal Bangalore, Srinath Vemuri, George D. Dangas Long B. Cao, Biykem Bozkurt, and Franz H. Messerli A6 THE AMERICAN JOURNAL OF CARDIOLOGY姞 VOL. 107 FEBRUARY 15, 2011 Patient Perception Versus Medical Record Entry of Cardiomyopathy Health-Related Conditions Among Patients With Relation of Pulse Pressure to Blood Pressure Heart Failure ..................................................569 Response to Exercise in Patients With Hypertrophic Adnan S. Malik, Grigorios Giamouzis, Cardiomyopathy .............................................600 Vasiliki V. Georgiopoulou, Lucy V. Fike, Kevin S. Heffernan, Martin S. Maron, Andreas P. Kalogeropoulos, Catherine R. Norton, Eshan A. Patvardhan, Richard H. Karas, and Dan Sorescu, Sidra Azim, Sonjoy R. Laskar, Jeffrey T. Kuvin, the Vascular Function Study Group Andrew L. Smith, Sandra B. Dunbar, and Javed Butler Editorial Effectiveness of Serial Increases in Amino-Terminal Clinical Challenges of Genotype Positive Pro–B-Type Natriuretic Peptide Levels to Indicate the (ⴙ)–Phenotype Negative (ⴚ) Family Members in Need for Mechanical Circulatory Support in Hypertrophic Cardiomyopathy .........................604 Children With Acute Decompensated Heart Barry J. Maron, Laura Yeates, and Failure ...........................................................573 Christopher Semsarian Derek T.H. Wong, Kristen George, Judith Wilson, Cedric Manlhiot, Brian W. McCrindle, Khosrow Adeli, Miscellaneous and Paul F. Kantor Usefulness of Repeated N-Terminal Pro-B-Type Arrhythmias and Conduction Natriuretic Peptide Measurements as Incremental Disturbances Predictor for Long-Term Cardiovascular Outcome After Vascular Surgery ....................................609 Relation of Obesity to Recurrence Rate and Burden Dustin Goei, Jan-Peter van Kuijk, Willem-Jan Flu, Sanne E. Hoeks, Michel Chonchol, of Atrial Fibrillation .........................................579 Hence J.M. Verhagen, Jeroen J. Bax, and Maya Guglin, Kuldeep Maradia, Ren Chen, and Don Poldermans Anne B. Curtis Usefulness of At Rest and Exercise Hemodynamics Roundtable Discussion (CME) to Detect Subclinical Myocardial Disease in Type 2 Diabetes Mellitus .............................................615 The Editor’s Roundtable: Implantable Cardioverter- Christine L. Jellis, Tony Stanton, Rodel Leano, Defibrillators in Primary Prevention of Sudden Jennifer Martin, and Thomas H. Marwick Cardiac Death and Disparity-Related Barriers to Implementation ...............................................583 Specific Characteristics of Sudden Death in a Vincent E. Friedewald, Gregg C. Fonarow, Mediterranean Spanish Population ...................622 Brian Olshansky, Clyde W. Yancy, and M. Teresa Subirana, Josep O. Juan-Babot, William C. Roberts Teresa Puig, Joaqu´ın Lucena, Antonio Rico, Manuel Salguero, Juan C. Borondo, Jorge Ordo´ñez, Valvular Heart Disease Josep Arimany, Rafael Va´zquez, Lina Badimon, Gaetano Thiene, and Antonio Baye´s de Luna Comparison of the Effectiveness and Safety of Low- Molecular Weight Heparin Versus Unfractionated Clinical and Prognostic Relevance of Heparin Anticoagulation After Heart Valve Echocardiographic Evaluation of Right Ventricular Surgery ..........................................................591 Geometry in Patients With Idiopathic Pulmonary Claudia Bucci, William H. Geerts, Andrew Sinclair, Arterial Hypertension ......................................628 and Stephen E. Fremes Stefano Ghio, Anna Sara Pazzano, Catherine Klersy, Laura Scelsi, Claudia Raineri, Rita Camporotondo, Congenital Heart Disease Andrea D’Armini, and Luigi Oltrona Visconti Seeking Optimal Relation Between Oxygen Clinically Significant Incidental Findings Among Saturation and Hemoglobin Concentration in Adults Human Immunodeficiency Virus-Infected Men With Cyanosis from Congenital Heart Disease ...595 During Computed Tomography for Determination of Craig S. Broberg, Ananda R. Jayaweera, Coronary Artery Calcium .................................633 Gerhard P. Diller, Sanjay K. Prasad, Swee Lay Thein, Nancy Crum-Cianflone, James Stepenosky, Bridget E. Bax, John Burman, and Sheila Medina, Dylan Wessman, David Krause, and Michael A. Gatzoulis Gilbert Boswell CONTENTS A11 Case Report Long-Term Follow Up of Atrioventricular Block in Transcatheter Aortic Valve Implantation ............641 Self-Terminated Ventricular Fibrillation and Recurrent Syncope ..........................................638 Instructions to Authors can be found at the AJC Yuval Konstantino, Angela Morello, website: www.AJConline.org Peter J. Zimetbaum, and Mark E. Josephson Classifieds on pages A10, A37 Readers’ Comments Comparison of 600 Versus 300-mg Clopidogrel Loading Dose in Patients With ST-Segment Elevation Full Text: www.ajconline.org Myocardial Infarction Undergoing Primary Coronary Angioplasty .....................................641 A18 THE AMERICAN JOURNAL OF CARDIOLOGY姞 VOL. 107 FEBRUARY 15, 2011 An Early and Simple Predictor of Severe Left Main and/or Three-Vessel Disease in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome Masami Kosuge, MD*, Toshiaki Ebina, MD, Kiyoshi Hibi, MD, Satoshi Morita, PhD, Mitsuaki Endo, MD, Nobuhiki Maejima, MD, Noriaki Iwahashi, MD, Kozo Okada, MD, Toshiyuki Ishikawa, MD, Satoshi Umemura, MD, and Kazuo Kimura, MD Clopidogrel should be initiated as soon as possible in patients with non–ST-segment elevation acute coronary syndrome (NSTE-ACS) except those who urgently require coro- nary artery bypass grafting (CABG). The present study assessed the ability to predict severe left main coronary artery and/or 3-vessel disease (LM/3VD) that would most likely require urgent CABG based on only clinical factors on admission in 572 patients with NSTE-ACS undergoing coronary angiography. Severe LM/3VD was defined as >75% stenosis of LM and/or 3VD with >90% stenosis in >2 proximal lesions of the left anterior descending coronary artery and other major epicardial arteries. Patients were divided into the 3 groups according to angiographic findings: no LM/3VD (n ⴝ 460), LM/3VD but not severe LM/3VD (n ⴝ 57), and severe LM/3VD (n ⴝ 55). Severe LM/3VD was associated with a higher rate of urgent CABG compared to no LM/3VD and LM/3VD but not severe LM/3VD (46%, 2%, and 2%, p <0.001). On multivariate analysis, degree of ST-segment elevation in lead aVR was the strongest predictor of severe LM/3VD (odds ratio 29.1, p <0.001), followed by positive troponin T level (odds ratio 1.27, p ⴝ 0.044). ST-segment elevation >1.0 mm in lead aVR best identified severe LM/3VD with 80% sensitivity, 93% specificity, 56% positive predictive value, and 98% negative predictive value. In conclusion, ST-segment elevation >1.0 mm in lead aVR on admission electrocardiogram is highly suggestive of severe LM/3VD in patients with NSTE-ACS. Selected patients with this finding might benefit from promptly undergoing angiography, withholding clopidogrel to allow early CABG. © 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107: 495–500) Dual antiplatelet therapy with clopidogrel and aspirin require urgent CABG, using only clinical factors on admis- should be initiated as soon as possible in patients with sion in patients with NSTE-ACS. non–ST-segment elevation acute coronary syndrome 1,2 (NSTE-ACS). However, such combination therapy can Methods increase perioperative bleeding in patients undergoing early 3–7 coronary artery bypass grafting (CABG). Therefore, one We studied 572 consecutive patients (mean age 67 ⫾ 11 might consider with-holding clopidogrel until coronary an- years, range 30 to 92, 397 men and 175 women) who were 8 giography and definition of the coronary anatomy. The admitted to Yokohama City University Medical Center proportion of patients with NSTE-ACS who undergo (Yokohama, Japan) coronary care unit and fulfilled the 4,5,8–12 CABG during hospitalization is 9% to 21%. CABG following criteria: (1) typical chest discomfort attributed to can often be deferred for several days, and few patients cardiac ischemia, lasting ⱖ5 minutes, occurring within 24 require urgent CABG. Ideally, clopidogrel should be with- hours before hospital admission, and involving an unstable held in the minority of patients who urgently require CABG pattern of pain including pain at rest, new onset, severe or and should be given to the remaining majority of patients. frequent angina, or accelerating angina14; (2) no conditions We previously examined clinical factors related to left main precluding evaluation ST-segment changes on electrocar- coronary artery and/or 3-vessel disease (LM/3VD) that diogram (ECG) such as left or right bundle branch block, would most likely lead to CABG in patients with NSTE- left ventricular hypertrophy, or ventricular pacing; (3) fully ACS but did not evaluate severity of coronary lesions in that assessable ECGs on admission; and (4) fully assessable 13 study. In the present study, we assessed the ability to angiographic data during hospitalization. We excluded pa- predict “severe” LM/3VD, which would most likely to tients with nonischemic or atypical pain, persistent new ST-segment elevation in leads other than lead aVR, recent (⬍6 months) percutaneous coronary intervention, or previ- Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan. Manuscript received August 28, 2010; revised manu- ous CABG. All patients gave informed consent. The study script received and accepted October 1, 2010. protocol was approved by the internal review board of *Corresponding author: Tel: 81-45-261-5656; fax: 81-45-261-9162. Yokohama City University Medical Center. E-mail address: 496 The American Journal of Cardiology (www.ajconline.org) Table 1 Clinical characteristics LM/3VD p Value No LM/3VD Nonsevere Severe (n ⫽ 460) (n ⫽ 57) (n ⫽ 55) Age (years) 66 ⫾ 11 69 ⫾ 10 68 ⫾ 11 0.06 Men 322 (70%) 39 (68%) 36 (66%) 0.78 Systolic blood pressure on admission (mm Hg) 150 ⫾ 25 150 ⫾ 32 141 ⫾ 26 0.07 Heart rate on admission (beats/min) 76 ⫾ 17 81 ⫾ 20 89 ⫾ 23 ⬍0.001 Killip class ⱖII on admission 26 (6%) 9 (16%) 17 (31%) ⬍0.001 Symptom onset ⱕ6 hours 356 (78%) 43 (75%) 49 (89%) 0.13 Previous myocardial infarction 86 (19%) 18 (32%) 12 (22%) 0.07 Previous percutaneous coronary intervention 90 (20%) 15 (26%) 5 (9%) 0.06 Risk factors Hypertension 304 (66%) 42 (74%) 38 (69%) 0.49 Diabetes mellitus 136 (30%) 29 (51%) 30 (55%) ⬍0.001 Smoking 229 (50%) 22 (39%) 23 (42%) 0.18 Hyperlipidemia* 230 (50%) 25 (44%) 29 (53%) 0.61 Family history of coronary artery disease 120 (26%) 13 (23%) 16 (29%) 0.75 Hemoglobin on admission (g/dl) 14 ⫾ 2 13 ⫾ 2 13 ⫾ 2 0.033 High-sensitivity C-reactive protein on admission (mg/dl) 0.131 (0.061–0.323) 0.180 (0.079–0.453) 0.253 (0.099–0.801) 0.005 Positive troponin T on admission 135 (29%) 28 (49%) 33 (60%) ⬍0.001 Creatine kinase-MB on admission (IU/L) 14 ⫾ 16 18 ⫾ 24 27 ⫾ 36 ⬍0.001 2 Estimated glomerular filtration rate on admission (ml/min/1.73 m ) 68 ⫾ 25 58 ⫾ 28 58 ⫾ 26 0.004 † Brain natriuretic peptide on admission (pg/ml) 67 (26–179) 187 (81–429) 230 (67–571) ⬍0.001 (n ⫽ 297) (n ⫽ 32) (n ⫽ 31) Cardiac procedures and outcomes at 30 days Death 1 (0.2%) 1 (2%) 2 (4%) 0.010 Myocardial (re)infarction 14 (3%) 3 (5%) 5 (9%) 0.23 Death/myocardial (re)infarction 15 (3%) 4 (7%) 7 (13%) 0.004 Urgent percutaneous coronary intervention 29 (6%) 7 (12%) 5 (9%) 0.22 Urgent coronary artery bypass surgery 7 (2%) 1 (2%) 25 (46%) ⬍0.001 Urgent revascularization (percutaneous coronary intervention or 36 (8%) 8 (14%) 30 (55%) ⬍0.001 coronary artery bypass surgery) Cardiac procedures Percutaneous coronary intervention 272 (59%) 36 (63%) 14 (25%) ⬍0.001 Coronary artery bypass surgery 27 (6%) 13 (23%) 40 (73%) ⬍0.001 Any revascularization (percutaneous coronary intervention or 291 (63%) 49 (86%) 54 (98%) ⬍0.001 coronary artery bypass surgery) Data are presented as mean ⫾ SD, median (interquartile range), or number of patients (percentage). * Fasting total cholesterol concentration ⱖ220 mg/dl, fasting triglyceride concentration ⱖ150 mg/dl, or use of antihyperlipidemic therapy. † Available for 360 patients. Table 2 Electrocardiographic findings Variable LM/3VD p Value No LM/3VD Nonsevere Severe (n ⫽ 460) (n ⫽ 57) (n ⫽ 55) ST-segment depression ⱖ0.5 mm 288 (63%) 53 (93%) 55 (100%) ⬍0.001 Maximal ST-segment depression (mm) 0.8 ⫾ 1.0 1.7 ⫾ 1.1 2.6 ⫾ 1.7 ⬍0.001 Sum of ST-segment depressions (mm) 2.6 ⫾ 3.6 6.7 ⫾ 5.1 10.5 ⫾ 7.3 ⬍0.001 Number of leads with ST-segment depression ⱖ0.5 mm 2.5 ⫾ 2.5 5.1 ⫾ 2.6 6.1 ⫾ 2.2 ⬍0.001 ST-segment elevation ⱖ0.5 mm in lead aVR 68 (15%) 39 (68%) 50 (91%) ⬍0.001 ST-segment elevation in lead aVR (mm) 0.1 ⫾ 0.3 0.6 ⫾ 0.5 1.2 ⫾ 0.7 ⬍0.001 Data are presented as mean ⫾ SD or number of patients (percentage). paper speed of 25 mm/s and an amplification of 10 mm/mV. ms after this point for ST-segment elevation using the preced- 15 All ECGs were examined by a single investigator who was ing TP segment as a baseline. ST-segment deviation was 14 blinded to all other clinical data. ST-segment shifts were mea- considered present if deviation was ⱖ0.5 mm in any lead. sured 80 ms after the J-point for ST-segment depression and 20 A qualitative assay for cardiac-specific troponin T (de- Coronary Artery Disease/Prediction of Severe LM/3VD in NSTE-ACS 497 tection limit 0.1 ng/ml of cardiac-specific troponin T; Roche Diagnostics, Tokyo, Japan) was performed on admission. Troponin T ⱖ0.1 ng/ml was defined as positive. Blood samples for measuring hemoglobin, plasma high-sensitivity C-reactive protein levels, and estimated glomerular filtra- tion rate were also taken on admission. Japanese equations were used to calculate estimated glomerular filtration rate 16 from serum creatinine level. Brain natriuretic peptide was simultaneously measured in 360 patients. Creatine ki- nase-MB levels were measured on admission, at 3-hour intervals during the first 24 hours, and in any patient with suspected reinfarction. All patients underwent cardiac catheterization a median of 3 days after admission. Urgent cardiac catheterization was performed in patients with unstable hemodynamics from ischemic attacks or with ischemic attacks that could not be controlled by intensive drug treatment. Type and timing of revascularization were left to the discretion of the treating physician. All coronary angiograms were evaluated by a single investigator who was blinded to all other clinical data. Stenosis ⱖ50% in the diameter of the LM or stenosis of ⱖ75% in ⱖ1 major epicardial vessel or its main branches was considered clinically significant. Severe LM/3VD was defined as (1) ⱖ75% stenosis of the LM, (2) 3VD with ⱖ90% stenosis of the proximal portion of the left anterior descending coronary artery and ⱖ90% stenosis of the right coronary artery and/or left circumflex coronary artery, and (3) definitions 1 and 2. Patients were categorize according to presence (n ⫽ 112) or absence (n ⫽ 460) of LM/3VD, and the former group was subdivided according to severity of coronary lesions: nonsevere LM/3VD (n ⫽ 57) and severe LM/3VD (n ⫽ 55). Demographic data, risk factors for coronary artery dis- ease, and data from physical examination on admission were collected. Major adverse events such as death, myo- cardial (re)infarction, or urgent revascularization were also recorded for all patients. Myocardial infarction was diag- nosed according to cardiac enzyme levels or electrocardio- graphic criteria. Enzymatic evidence of myocardial infarc- tion was defined as an increase of creatine kinase-MB to higher than the upper limit of normal if the previous creatine kinase-MB level was in the normal range or 50% above the previous level if the previous level was above the normal 17 range. Electrocardiographic evidence of myocardial in- farction was defined as new clinically significant Q waves in ⱖ2 contiguous leads distinct from the enrollment myocar- 17 dial infarction. Patients were followed for 30 days after admission. Figure 1. Representative electrocardiogram of a patient with severe left Results are expressed as mean ⫾ SD or as frequency main coronary artery and/or 3-vessel disease. Troponin T was positive on (percentage), and high-sensitivity C-reactive protein and admission. ST-segment elevation in lead aVR was 4.5 mm on admission brain natriuretic peptide levels are expressed as median and electrocardiogram. Urgent coronary angiography showed 90% stenosis of interquartile range. Data were compared by 1-way analysis the left main trunk. of variance, Kruskal-Wallis test, and chi-square analysis. Differences were considered statistically significant at p tified on multivariate analysis were determined. SPSS sta- value ⬍0.05. Multivariate logistic regression analysis was tistical software (SPSS, Inc., Chicago, Illinois) was used for used to identify clinical predictors of severe LM/3VD all analyses. among the variables associated (p ⬍0.05) with this diagno- sis on univariate analysis. Odds ratios and 95% confidence Results intervals were calculated. In addition, sensitivity, specific- ity, positive predictive value, negative predictive value, and Baseline characteristics are listed in Table 1. Patients predictive accuracy of predictors of severe LM/3VD iden- with LM/3VD, especially severe LM/3VD, had a more 498 The American Journal of Cardiology (www.ajconline.org) Table 3 Univariate and multivariate predictors of severe left main coronary artery and/or three-vessel disease Variable Odds Ratio (95% CI) p Value Univariate Multivariate Systolic blood pressure 0.020 0.07 Heart rate ⬍0.001 0.29 Killip class ⱖII ⬍0.001 0.29 Previous percutaneous coronary intervention 0.045 0.80 Diabetes mellitus 0.001 0.08 High-sensitivity C-reactive protein ⬍0.001 0.30 Positive troponin T 1.27 (1.10–2.78) ⬍0.001 0.044 Creatine kinase-MB ⬍0.001 0.33 Estimated glomerular filtration rate ⬍0.001 0.32 Maximal ST-segment depression ⬍0.001 0.053 Sum of ST-segment depressions ⬍0.001 0.055 Number of leads with ST-segment depression ⱖ0.5 mm ⬍0.001 0.24 Degree of ST-segment elevation in lead aVR 29.1 (9.54–49.8) ⬍0.001 ⬍0.001 CI ⫽ confidence interval. Table 4 and predictive accuracy of ST-segment elevation in lead Comparison of ST-segment elevation in lead aVR and positive troponin aVR and positive troponin T for severe LM/3VD are pre- T for predicting severe left main coronary artery and/or three-vessel sented in Table 4. ST-segment elevation ⱖ1.0 mm in lead disease aVR best identified severe LM/3VD. Sensitivity Specificity PPV NPV Predictive Accuracy Discussion ST-segment elevation in lead aVR Our study showed that ST-segment elevation ⱖ1.0 mm † † † ⱖ0.5 mm 91% 79% 32% 99% 80% in lead aVR and positive troponin T on admission (espe- ⱖ1.0 mm 80% 93% 56% 98% 92% cially the former) were highly suggestive of severe LM/ † † † ⱖ1.5 mm 27% 98% 58% 93% 91% 3VD, and the converse was also true, i.e., absence of these † † † † Positive troponin T 60%* 69% 17% 94% 68% findings was rarely associated with severe LM/3VD. To our knowledge, this is the first study to establish a reliable NPV ⫽ negative predictive value; PPV ⫽ positive predictive value. * p ⬍0.05; † p ⬍0.01 versus ST-segment elevation ⱖ1.0 mm in lead technique for early identification of patients with severe aVR. LM/3VD who are most likely to require urgent CABG in patients with NSTE-ACS. Our findings have important im- plications for identification of high-risk patients and selec- rapid heart rate, higher prevalences of Killip class ⱖII, tion of optimal treatment strategy in the setting of NSTE- diabetes mellitus, positive troponin T, and higher levels of ACS. high-sensitivity C-reactive protein, creatine kinase-MB, and The standard 12-lead ECG, which is an inexpensive, brain natriuretic peptide than did patients without LM/3VD. noninvasive, and readily available clinical tool, has a central LM/3VD was associated with lower levels of hemoglobin role in diagnosis and immediate triage for NSTE-ACS and and estimated glomerular filtration rate. There were no sig- provides important prognostic information. In particular, nificant differences in other clinical variables among the 3 presence of ST-segment depression on admission ECG has groups. been recognized to be a strong predictor of adverse out- 14,17–20 Urgent CABG was more frequently done in patients with comes in patients with NSTE-ACS. The Global Uti- severe LM/3VD (46%). In contrast, urgent CABG was done lization of Strategies to Open Occluded Arteries in Acute in only 2% of patients with LM/3VD but not severe LM/ Coronary Syndrome IV (GUSTO-IV ACS) trial of 7,800 3VD. patients with NSTE-ACS has highlighted the striking prog- Electrocardiographic findings are presented in Table 2. nostic value of ST-segment depression on admission com- Compared to patients without LM/3VD, those with LM/ pared to expanded biomarker profiles and traditional risk 18 3VD, especially severe LM/3VD, had a higher prevalence factors. However, most previous studies assessing the and a larger amount of ST-segment depression, a larger clinical significance of admission ECG in patients with number of leads other than lead aVR with ST-segment NSTE-ACS have focused on ST-segment deviation in leads depression, and a higher prevalence and greater magnitude other than lead aVR; i.e., clinicians have used an “11-lead” of ST-segment elevation in lead aVR. Figure 1 shows a ECG, neglecting lead aVR. representative ECG of a patient with severe LM/3VD. Several studies have found that analysis of lead aVR is 13,15,21,22 In multivariate models, degree of ST-segment elevation useful for evaluation of NSTE-ACS. Gorgels et 21 in lead aVR was the strongest predictor of severe LM/3VD, al reported that ST-segment elevation in lead aVR accom- followed by positive troponin T (Table 3). Sensitivity, spec- panied by ST-segment depression in leads I, II, and V to V 4 6 ificity, positive predictive value, negative predictive value, during episodes of angina strongly suggests LM/3VD in Coronary Artery Disease/Prediction of Severe LM/3VD in NSTE-ACS 499 15 patients with angina at rest. Barrabés et al demonstrated ST-segment depression in other leads in patients with that presence of ST-segment elevation in lead aVR predicts NSTE-ACS. risk of in-hospital death in patients with a first non–ST- Recently approved antiplatelet agents such as prasugrel segment elevation acute myocardial infarction. In that and ticagrelor, a new reversible agent, have been shown to study, ST-segment elevation in lead aVR was also related to decrease ischemic events compared to clopidogrel, but the 7 LM/3VD; however, coronary angiography was performed former increased the risk of perioperative bleeding and the 26 in only 56% of subjects within 6 months after infarction. We latter did not decrease the risk of perioperative bleeding. previously demonstrated that presence of ST-segment ele- Until an antiplatelet agent that decreases ischemic events vation ⱖ0.5 mm in lead aVR on admission ECG strongly and decreases perioperative bleeding compared to clopi- suggested LM/3VD and had a higher prognostic value than dogrel becomes available, some patients will be exposed to ST-segment depression in other leads in patients with a risk of urgent CABG-related bleeding caused by upstream NSTE-ACS who underwent coronary angiography in the dual antiplatelet therapy. 13,22 acute phase. However, previous studies, including ours, This study was retrospective, performed at a single cen- did not consider severity of LM/3VD, which has clinical ter, and included a small number of patients who underwent implications for timing of CABG in relation to dual anti- coronary angiography during hospitalization. However, the platelet therapy. An increased risk of perioperative bleeding proportion of patients undergoing CABG during hospital- events due to early clopidogrel administration is clinically ization in this study (14%) was similar to that in previous 4,10,12 problematic in patients with LM/3VD who urgently require studies. Moreover, because our subjects underwent CABG. In such patients, postponing CABG for several days cardiac catheterization a median of 3 days after admission, might seriously compromise outcomes. Timing of CABG our data on clinical outcomes according to angiographic depends on many factors including severity of coronary findings cannot be generalized to hospitals that provide lesions, risk of ongoing ischemia, general condition of a early invasive strategies. Further studies in larger numbers patient, bleeding risk associated with upstream antithrom- of patients are needed to verify our results. botic therapies, and local logistic factors such as collocation of cardiac surgical services and surgical waiting lists. The 1. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE II, Fesmire FM, Hochman JS, Levin TN, Lincoff present study examined predictors of patients with severe AM, Peterson ED, Theroux P, Wenger NK, Wright RS, Smith SC Jr, LM/3VD likely to require urgent CABG, considering the Jacobs AK, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle coronary anatomy. We demonstrated that ST-segment ele- BW, Nishimura R, Ornato JP, Page RL, Riegel B. ACC/AHA guide- vation ⱖ1.0 mm in lead aVR was the most accurate pre- lines for the management of patients with unstable angina/non–ST- dictor of severe LM/3VD. However, its positive predictive segment elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association task force on prac- value was 56%, which was moderate. More importantly, the tice guidelines (writing committee to revise the 2002 guidelines for the negative predictive value of ST-segment elevation ⱖ1.0 management of patients with unstable angina/non-st-elevation myo- mm in lead aVR for detection of severe LM/3VD was 98%, cardial infarction). Circulation 2007;116:803–877. which was very high. Absence of this finding was rarely 2. Bassand JP, Hamm CW, Ardissino D, Boersma E, Budaj A, Fernán- dez-Avilés F, Fox KA, Hasdai D, Ohman EM, Wallentin L, Wijns W. associated with severe LM/3VD. If ST-segment elevation Guidelines for the diagnosis and treatment of non-ST-segment eleva- ⱖ1.0 mm in lead aVR is absent, treatment with upstream tion acute coronary syndromes. The task force for the diagnosis and clopidogrel is strongly recommended. 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