Supplementary Appendix

Transcription

1 Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Feldman T, Foster E, Glower DG, et al. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med 2011;364: DOI: /NEJMoa (PDF updated May 11, 2011.)

2 APPENDIX List of study contributors Core Quantitative Echocardiographic Laboratory Director: University of California at San Francisco Elyse Foster Technical Director: San Francisco, CA Esperanza Viloria Study Sites Ted Feldman John Alexander, Edgar G. Chedrawy Mark B. Lampert, Steven Smart, Alan Zunamon Claudia Focks, Dale Seifert, Beth Garnier Andrew Wang Donald Glower, Carmelo Milano James Jollis, Thomas Ryan Dana Glisson, Aretha Herron, Sophie Wang Timothy Byrne Pierre Tibi, H. Kenith Fang J. Michael Morgan Gabriella Diaz, Hope Mangum NorthShore University HealthSystem Evanston, IL Duke University Durham, NC Banner Good Samaritan Medical Center Phoenix, AZ

3 Ramon Quesada Niberto Moreno Rafael Machado Research Coordinator: Maria Ines Aridid Paul Grayburn, Azam Anwar Baron Hamman, Robert F. Hebeler, Paul Grayburn Susan Aston Andy Eisenhauer Larry Cohn, Michael Davidson Judy Mangion, Justina Wu Denise Cinamon, Tina Sampong James Hermiller Keith Allen, Dave Heimansohn John Bates, Douglas Segar, Charles Taliercio Research Coordinator: Anne Taylor Baptist Hospital of Miami Miami, FL Baylor University Medical Center Dallas, TX Brigham and Women s Hospital Boston, MA The Care Group Indianapolis, IN

4 Michael J. Rinaldi Eric Skipper, Robert M. Steigel Geoffrey Rose Gale Schwarz, Tiffany Michel Saibal Kar, Raj Makkar Alfredo Trento, Wen Cheng, Gregory Fontana, Robert Kass Robert Siegel, Kirsten Tolstrup, Tasneem Naqvi Kelly Davis, Asma Hussaini, Diana Remba Patrick Whitlow, Samir Kapadia, E. Murat Tuzcu Marc Gillinov, Tomislav Mihaljevic Leonardo Rodriquez, William Stewart Kelly Brezina, Lisa Rittwage Carolinas Medical Center Charlotte, NC Cedars-Sinai Medical Center Los Angeles, CA The Cleveland Clinic Cleveland, OH

5 William Gray, Allan Schwartz, Hal Wasserman Michael Argenziano, Yoshifumi Naka, Craig Smith, Allan Stewart, Mathew Williams Shunichi Homma, Roy Pizzarello, Linda Gillam, Becky Hahn, Neil Goyal Edie Escala, Mafo Kamanda-Kosseh, Miriam Lucca-Susana Vasilis Babaliaros, Ziyad Ghazzal Thomas Vassiliades Omar Latouff, John Puskas Stamatios Lerakis, Stephen Clements, Randolph Martin, John Merlino Research Coordinator: Pamela Hyde Brian Whisenant Stephen Clayson Steven C. Horton Research Coordinator: Eric Johnson Columbia University New York, NY; Danville, CT Emory University Hospital Atlanta, GA Latter Day Saints Hospital Salt Lake City, UT

6 Richard Smalling George Letsou, Jon-Cecil Walkes Catalin Loghin, Andrew Hamilton Mary Vooletich, Pallavi Ahobila-Vajjula Wes Pedersen Frazier Eates, Tom Flavin, Timothy Kroshus, Vibhu Kshettry Richard Bae, Kevin Harris, Desmond Jay Sara Olson, Peg Demmer Omar Nass Deepak Gangahar, R. Kent Jex Kaliprasad Ayala Research Coordinator: Susan Krenk S. Chiu Wong, Geoffrey Bergman Leonard Girardi, O. Wayne Isom, Karl Krieger, Arash Salemi, Nickolas Skubas Richard Devereux Research Coordinator: Dolores T. Reynolds Memorial Hermann Heart and Vascular Institute/UTHealth Houston, TX Minneapolis Heart Institute Minneapolis, MN Nebraska Heart Institute Lincoln, NE New York Presbyterian Hospital New York, NY

7 James Slater Aubrey Galloway Itzhak Kronzon, Gila Perk Karen Hager, Elise Weisman, Cindy Lau-Yan Yung Stephen Ramee Eugene Parrino Yvonne Gilliland, Sangeeta Shah Barbara Hirstius, Laurie Ventura Robert Kipperman, Mohammad Ghani R. Mark Bodenhamer, Scott Lucas, John Randolph John Williams Stacie Hanes Raymond Leung Roderick MacArthur, John Mullen, David Ross Jonathan Choy, Alan Jones, Dylan Taylor, Randall Williams Linda Kvill, Anna Law NYU Medical Center New York, NY Ochsner Clinic Foundation New Orleans, LA Oklahoma Heart Hospital Oklahoma City, OK Royal Alexandra Hospital Edmonton, AB, Canada

8 Paul Kramer Brian Castlemain, Andrew Schwartz Linda Crouse, Carrie Totta Millie Salkind, Tawny Willson Andrew Berke Roberto Colangelo, Paul Damus, Harold Fernandez, Newell Robinson, James Taylor Aasha Gopal, Alan Katz, Dennis Mihalatos Elizabeth Haag, Jeannette McLaughlin, Aracely Norales Mansoor Qureshi Andrew Pruitt, Bobby Kong Benjamin McAllister, Steven Girard Research Coordinator: Carol Carulli Tanvir Bajwa, Suhail Allaqaband David Kress, Daniel O Hair Kiran Sagar Research Coordinator: Susan Oxborough Shawnee Mission Medical Center Shawnee Mission, KS St. Francis Hospital Long Island, NY St. Joseph s Mercy Hospital Ypsilanti, MI St. Luke s Medical Center Milwaukee, WI

9 James T. Maddux, Mark Sanz Stephen Tahta, Matthew Maxwell Bradley Berry, Joseph Knapp Research Coordinator: Heidi Boehm Mark Reisman David Gartman, Joseph Teply Amish Desai, Kier Huehnergarth, Kimberly Krabill Research Coordinator: Inger Rasmussen Peter Fail Tommy Fudge, Kerry Paape, Michael Trotter Eric Engeron Monique Robert, Deanna K. Benoit Eric Horlick Tirone David Melitta Mezody Research Coordinator: Kristeen Chamberlain St. Patrick s Hospital & Health Science Ctr Missoula, MT Swedish Medical Center Seattle, WA Terrebonne General Medical Center Houma, LA Toronto General Hospital Toronto, ON, Canada

10 Reginald Low, Jason Rogers J. Nilas Young, Kuppe Shankar William Bommer, Thomas Smith, Sandhya Venugopal Kimberly Book, Kori Harder John D. Carroll Joseph Cleveland, David Fullerton Robert Quaife, Ernesto Salcedo Research Coordinator: Kelly Jones Howard Herrmann Michael Acker, Y. Joseph Woo Frank E. Silvestry, Susan E. Wiegers Judi Willhide, Terry Mannion Steven R. Bailey John Calhoun, Edward Sako John Erikson Research Coordinator: Gus Banda University of California at Davis Sacramento, CA University of Colorado Health Sciences Center Denver, CO University of Pennsylvania Philadelphia, PA University of Texas Health Sciences Ctr San Antonio, TX

11 D. Scott Lim Irving L. Kron John Dent Research Coordinator: Linda Bailes Eric Fretz John G. Ofiesh Manjeet Mann Research Coordinator: Liz Martin Kenneth Kent, Lowell Satler, Augusto Pichard Ammar Bafi, Steven Boyce Pamela Sears-Rogan, Stephen Goldstein Research Coordinator: Petros Okubagzi John Lasala Marc Moon, Ralph Damiano Benicio Barzilai, Brian Lindman, Jose Madrazo, Alan Zajarias Michelle Myers, Kim Striler University of Virginia Charlottesville, VA Victoria Heart Institute Foundation Victoria BC, Canada Washington Hospital Center Washington DC Washington University Medical Center St. Louis, MO

12 George Hanzel Marc Sakwa, Francis Shannon Michael Gallagher, Pamela Markovitz,, Amr Abbas Research Coordinator: Hong Huang William Beaumont Hospital Royal Oak, MI

13 Supplementary Material Supplementary Table 1: Baseline Characteristics, Per Protocol Population Characteristic n (%) N Percutaneous (N = 137) N Surgery (N = 80) p-value Age (years) ± ± > 75 years of age (30.7%) (23.8%) 0.35 Male Gender (62.0%) (66.3%) 0.56 Coronary Artery Disease (46.3%) (43.8%) 0.78 Prior Myocardial infarction (18.4%) (21.5%) 0.60 Atrial fibrillation (34.1%) (38.7%) 0.55 Diabetes (9.5%) 80 7 (8.8%) 0.99 Chronic Obstructive (16.2%) (13.8%) 0.70 Pulmonary Disease Prior Coronary artery (18.2%) (16.3%) 0.85 bypass graft Prior Percutaneous (23.5%) (16.3%) 0.23 Intervention Left ventricular ejection ± ± fraction NYHA Functional Class I 11 (8.0%) 14 (17.5%) II 54 (39.4%) 26 (32.5%) III 62 (45.3%) 36 (45.0%)

14 Characteristic n (%) N Percutaneous (N = 137) N Surgery (N = 80) p-value IV 10 (7.3%) 4 (5.0%) MR Severity to 2+: Mild-to- 0 (0.0%) 1 (1.3%) Moderate 2+: Moderate 6 (4.4%) 5 (6.3%) 3+: Moderate-to-Severe 108 (78.8%) 56 (70.0%) 4+: Severe 23 (16.8%) 18 (22.5%) MR Regurgitant Volume ± ± (ml/beat) MR Regurgitant Orifice ± ± Area (cm²) MR Etiology Functional 39 (28.5%) 18 (22.5%) Degenerative with 40 (29.2%) 22 (27.5%) Anterior/Bileaflet Flail/Prolapse Degenerative with 53 (38.7%) 38 (47.5%) Posterior Flail/Prolapse Degenerative with 5 (3.6%) 2 (2.5%) Neither Flail nor Prolapse

15 Supplementary Table 2A: Additional Intention to Treat Analysis Cohort: Comparison of Strategies. Event Percutaneous (N =175) Surgical (N = 89) p-value Death 11 (6.3%) 5 (5.6%) 1.0 Surgery for Mitral Valve 9 (5.1%) 2 (2.2%) 0.43 Dysfunction MR 3+ or (21.7%) 18 (20.2%) 0.90 Freedom from Death, 118 (67.4%) 65 (73.0%) 0.42** Surgery for Mitral Valve Dysfunction, 3+ or 4+ MR at 12 months* First mitral valve surgery in percutaneous arm vs re-operation for mitral valve dysfunction in surgical arm *Component rates do not sum to rate of composite because of the possibility of more than one event per patient. **p value for difference between treatment groups (p value for exclusion of prespecified effectiveness margin, 0.001)

16 2B: Per Protocol Analysis Cohort Event Percutaneous (N = 134) Surgical (N = 74) p-value Death 6 (4.5%) 5 (6.8%) 0.70 Surgery for Mitral Valve 9 (6.7%) 2 (2.7%) 0.36 Dysfunction MR 3+ or (17.2%) 3 (4.1%) 0.01 Freedom from Death, 97 (72.4%) 65 (87.8%) 0.02** Surgery for Mitral Valve Dysfunction, 3+ or 4+ MR at 12 months* First mitral valve surgery in percutaneous arm vs re-operation for mitral valve dysfunction in surgical arm *Component rates do not sum to rate of composite because of the possibility of more than one event per patient. **p value for difference between treatment groups (p value for exclusion of prespecified effectiveness margin, 0.001)

17 Supplementary Table 3: Per-Protocol Analysis of Major Adverse Events at 30 days. n (%) Event Percutaneous (N = 136) Surgical (N = 79) p-value Death 0 (0.0%) 2 (2.5%) 0.26 Myocardial infarction 0 (0.0%) 0 (0.0%) NA Re-operation for failed surgical 0 (0.0%) 1 (1.3%) 0.78 repair or replacement Urgent or emergent cardiovascular 0 (0.0%) 4 (5.1%) 0.03 surgery for adverse events Major Stroke 0 (0.0%) 2 (2.5%) 0.26 Renal Failure 0 (0.0%) 0 (0.0%) NA Deep wound infection 0 (0.0%) 0 (0.0%) NA Ventilation > 48 hours 0 (0.0%) 4 (5.1%) 0.03 GI complication requiring surgery 1 (0.7%) 0 (0.0%) 1.00 New onset of persistent AF 0 (0.0%) 0 (0.0%) NA Septicemia 0 (0.0%) 0 (0.0%) NA Transfusion of 2 units of blood 12 (8.8%) 42 (53.2%) <0.001 Any MAE* (%) 13 (9.6%) 45 (57.0%) <0.001 Any MAE excluding transfusion* 1 (0.7%) 9 (11.4%) (%) * Component rates do not sum to to rate of composite because of the possibility of more than one event per patient.

18 Supplementary Table 4: Serious adverse events according to site report, not CEC adjudicated Percutaneous (N=184 Surgery (N=95 All Patients (N=279 Any SAE 93 (50.5%) 46 (48.4%) 139 (49.8%) BLOOD AND LYMPHATIC 12 (6.5%) 3 (3.2%) 15 (5.4%) SYSTEM DISORDERS ANAEMIA OF CHRONIC 1 (0.5%) 0 (0.0%) 1 (0.4%) DISEASE ANAEMIA 11 (6.0%) 3 (3.2%) 14 (5.0%) CARDIAC DISORDERS 51 (27.7%) 24 (25.3%) 75 (26.9%) ANGINA PECTORIS 2 (1.1%) 1 (1.1%) 3 (1.1%) ARRHYTHMIA 1 (0.5%) 2 (2.1%) 3 (1.1%) ATRIAL FIBRILLATION 20 (10.9%) 9 (9.5%) 29 (10.4%) ATRIAL FLUTTER 3 (1.6%) 2 (2.1%) 5 (1.8%) ATRIAL TACHYCARDIA 2 (1.1%) 0 (0.0%) 2 (0.7%) ATRIAL THROMBOSIS 1 (0.5%) 0 (0.0%) 1 (0.4%) ATRIOVENTRICULAR BLOCK 3 (1.6%) 0 (0.0%) 3 (1.1%) COMPLETE ATRIOVENTRICULAR BLOCK 1 (0.5%) 1 (1.1%) 2 (0.7%) BRADYCARDIA 2 (1.1%) 0 (0.0%) 2 (0.7%) CARDIAC ARREST 2 (1.1%) 0 (0.0%) 2 (0.7%)

19 Percutaneous (N=184 Surgery (N=95 All Patients (N=279 CARDIAC FAILURE 6 (3.3%) 7 (7.4%) 13 (4.7%) CONGESTIVE CARDIAC PERFORATION 1 (0.5%) 0 (0.0%) 1 (0.4%) CARDIAC TAMPONADE 3 (1.6%) 1 (1.1%) 4 (1.4%) CARDIO-RESPIRATORY 1 (0.5%) 0 (0.0%) 1 (0.4%) ARREST CARDIOGENIC SHOCK 0 (0.0%) 1 (1.1%) 1 (0.4%) CARDIOMYOPATHY 1 (0.5%) 0 (0.0%) 1 (0.4%) CHORDAE TENDINAE 1 (0.5%) 0 (0.0%) 1 (0.4%) RUPTURE CONDUCTION DISORDER 0 (0.0%) 1 (1.1%) 1 (0.4%) INTRACARDIAC THROMBUS 0 (0.0%) 1 (1.1%) 1 (0.4%) MITRAL VALVE DISEASE 1 (0.5%) 0 (0.0%) 1 (0.4%) MITRAL VALVE 23 (12.5%) 3 (3.2%) 26 (9.3%) INCOMPETENCE MYOCARDIAL INFARCTION 1 (0.5%) 0 (0.0%) 1 (0.4%) NODAL ARRHYTHMIA 0 (0.0%) 1 (1.1%) 1 (0.4%) NODAL RHYTHM 0 (0.0%) 3 (3.2%) 3 (1.1%) PERICARDIAL EFFUSION 6 (3.3%) 4 (4.2%) 10 (3.6%) SINUS ARRHYTHMIA 1 (0.5%) 1 (1.1%) 2 (0.7%)

20 Percutaneous (N=184 Surgery (N=95 All Patients (N=279 SINUS BRADYCARDIA 1 (0.5%) 1 (1.1%) 2 (0.7%) SINUS TACHYCARDIA 1 (0.5%) 0 (0.0%) 1 (0.4%) SUPRAVENTRICULAR 1 (0.5%) 0 (0.0%) 1 (0.4%) TACHYCARDIA TRICUSPID VALVE 0 (0.0%) 1 (1.1%) 1 (0.4%) INCOMPETENCE VENTRICULAR DYSFUNCTION 1 (0.5%) 1 (1.1%) 2 (0.7%) VENTRICULAR FIBRILLATION 1 (0.5%) 2 (2.1%) 3 (1.1%) VENTRICULAR TACHYCARDIA 4 (2.2%) 2 (2.1%) 6 (2.2%) CONGENITAL, FAMILIAL AND 2 (1.1%) 0 (0.0%) 2 (0.7%) GENETIC DISORDERS ATRIAL SEPTAL DEFECT 2 (1.1%) 0 (0.0%) 2 (0.7%) EAR AND LABYRINTH 1 (0.5%) 0 (0.0%) 1 (0.4%) DISORDERS VERTIGO 1 (0.5%) 0 (0.0%) 1 (0.4%) EYE DISORDERS 0 (0.0%) 1 (1.1%) 1 (0.4%) RETINAL ARTERY EMBOLISM 0 (0.0%) 1 (1.1%) 1 (0.4%) GASTROINTESTINAL 10 (5.4%) 2 (2.1%) 12 (4.3%) DISORDERS ABDOMINAL PAIN 1 (0.5%) 1 (1.1%) 2 (0.7%)

21 Percutaneous (N=184 Surgery (N=95 All Patients (N=279 COLONIC POLYP 1 (0.5%) 0 (0.0%) 1 (0.4%) DYSPHAGIA 1 (0.5%) 0 (0.0%) 1 (0.4%) GASTRITIS HAEMORRHAGIC 1 (0.5%) 0 (0.0%) 1 (0.4%) GASTROINTESTINAL 1 (0.5%) 1 (1.1%) 2 (0.7%) HAEMORRHAGE HAEMATOCHEZIA 1 (0.5%) 0 (0.0%) 1 (0.4%) ILEUS PARALYTIC 1 (0.5%) 0 (0.0%) 1 (0.4%) INTESTINAL PERFORATION 1 (0.5%) 0 (0.0%) 1 (0.4%) NAUSEA 1 (0.5%) 0 (0.0%) 1 (0.4%) PERITONITIS 1 (0.5%) 0 (0.0%) 1 (0.4%) RECTAL HAEMORRHAGE 2 (1.1%) 0 (0.0%) 2 (0.7%) SMALL INTESTINAL 1 (0.5%) 0 (0.0%) 1 (0.4%) OBSTRUCTION VOMITING 1 (0.5%) 0 (0.0%) 1 (0.4%) GENERAL DISORDERS AND 14 (7.6%) 5 (5.3%) 19 (6.8%) ADMINISTRATION SITE CONDITIONS ADVERSE DRUG REACTION 2 (1.1%) 0 (0.0%) 2 (0.7%) ASTHENIA 1 (0.5%) 0 (0.0%) 1 (0.4%) CHEST PAIN 1 (0.5%) 0 (0.0%) 1 (0.4%)

22 Percutaneous (N=184 Surgery (N=95 All Patients (N=279 DEATH 5 (2.7%) 1 (1.1%) 6 (2.2%) HEPARIN-INDUCED 0 (0.0%) 1 (1.1%) 1 (0.4%) THROMBOCYTOPENIA INJECTION SITE 4 (2.2%) 0 (0.0%) 4 (1.4%) HAEMORRHAGE NECROSIS 1 (0.5%) 0 (0.0%) 1 (0.4%) NON-CARDIAC CHEST PAIN 1 (0.5%) 1 (1.1%) 2 (0.7%) OEDEMA PERIPHERAL 1 (0.5%) 0 (0.0%) 1 (0.4%) PYREXIA 0 (0.0%) 2 (2.1%) 2 (0.7%) SYSTEMIC INFLAMMATORY 1 (0.5%) 0 (0.0%) 1 (0.4%) RESPONSE SYNDROME HEPATOBILIARY DISORDERS 3 (1.6%) 0 (0.0%) 3 (1.1%) CHOLECYSTITIS ACUTE 1 (0.5%) 0 (0.0%) 1 (0.4%) CHOLECYSTITIS 1 (0.5%) 0 (0.0%) 1 (0.4%) CHOLELITHIASIS 1 (0.5%) 0 (0.0%) 1 (0.4%) INFECTIONS AND 16 (8.7%) 7 (7.4%) 23 (8.2%) INFESTATIONS BRONCHITIS 0 (0.0%) 1 (1.1%) 1 (0.4%) CELLULITIS 1 (0.5%) 0 (0.0%) 1 (0.4%) CLOSTRIDIUM COLITIS 1 (0.5%) 1 (1.1%) 2 (0.7%)

23 Percutaneous (N=184 Surgery (N=95 All Patients (N=279 DIVERTICULITIS 1 (0.5%) 0 (0.0%) 1 (0.4%) ENDOCARDITIS 2 (1.1%) 0 (0.0%) 2 (0.7%) EPIGLOTTITIS 0 (0.0%) 1 (1.1%) 1 (0.4%) GANGRENE 1 (0.5%) 0 (0.0%) 1 (0.4%) GASTROENTERITIS 0 (0.0%) 1 (1.1%) 1 (0.4%) GROIN INFECTION 1 (0.5%) 0 (0.0%) 1 (0.4%) INFECTION 1 (0.5%) 0 (0.0%) 1 (0.4%) PNEUMONIA 5 (2.7%) 4 (4.2%) 9 (3.2%) SEPSIS SYNDROME 1 (0.5%) 0 (0.0%) 1 (0.4%) SEPSIS 1 (0.5%) 1 (1.1%) 2 (0.7%) STAPHYLOCOCCAL 0 (0.0%) 1 (1.1%) 1 (0.4%) INFECTION STAPHYLOCOCCAL SEPSIS 1 (0.5%) 0 (0.0%) 1 (0.4%) STREPTOCOCCAL SEPSIS 0 (0.0%) 1 (1.1%) 1 (0.4%) TOOTH ABSCESS 1 (0.5%) 0 (0.0%) 1 (0.4%) URINARY TRACT INFECTION 1 (0.5%) 0 (0.0%) 1 (0.4%) VIRAL INFECTION 1 (0.5%) 0 (0.0%) 1 (0.4%) INJURY, POISONING AND 19 (10.3%) 7.4% (7/95) 26 (9.3%) PROCEDURAL COMPLICATIONS ANAEMIA POSTOPERATIVE 1 (0.5%) 1 (1.1%) 2 (0.7%)

24 Percutaneous (N=184 Surgery (N=95 All Patients (N=279 ANAESTHETIC 0 (0.0%) 1 (1.1%) 1 (0.4%) COMPLICATION NEUROLOGICAL CARDIAC PACEMAKER 1 (0.5%) 0 (0.0%) 1 (0.4%) MALFUNCTION CARDIAC PROCEDURE 0 (0.0%) 1 (1.1%) 1 (0.4%) COMPLICATION CONCUSSION 1 (0.5%) 0 (0.0%) 1 (0.4%) DEVICE DISLOCATION 1 (0.5%) 0 (0.0%) 1 (0.4%) DEVICE FAILURE 1 (0.5%) 0 (0.0%) 1 (0.4%) DEVICE MALFUNCTION 1 (0.5%) 0 (0.0%) 1 (0.4%) FRACTURE 1 (0.5%) 0 (0.0%) 1 (0.4%) FROSTBITE 1 (0.5%) 0 (0.0%) 1 (0.4%) HAEMOTHORAX 1 (0.5%) 1 (1.1%) 2 (0.7%) HEAD INJURY 1 (0.5%) 0 (0.0%) 1 (0.4%) HIP FRACTURE 1 (0.5%) 1 (1.1%) 2 (0.7%) PHARYNGEAL INJURY 1 (0.5%) 0 (0.0%) 1 (0.4%) POLYTRAUMATISM 1 (0.5%) 0 (0.0%) 1 (0.4%) POST PROCEDURAL 5 (2.7%) 1 (1.1%) 6 (2.2%) HAEMORRHAGE

25 Percutaneous (N=184 Surgery (N=95 All Patients (N=279 POSTPERICARDIOTOMY 0 (0.0%) 1 (1.1%) 1 (0.4%) SYNDROME SKIN LACERATION 1 (0.5%) 0 (0.0%) 1 (0.4%) SPINAL FRACTURE 1 (0.5%) 0 (0.0%) 1 (0.4%) THROMBOSIS IN DEVICE 1 (0.5%) 0 (0.0%) 1 (0.4%) VASCULAR INJURY 0 (0.0%) 1 (1.1%) 1 (0.4%) WOUND COMPLICATION 1 (0.5%) 0 (0.0%) 1 (0.4%) WOUND SECRETION 1 (0.5%) 0 (0.0%) 1 (0.4%) INVESTIGATIONS 2 (1.1%) 1 (1.1%) 3 (1.1%) HAEMOGLOBIN DECREASED 1 (0.5%) 0 (0.0%) 1 (0.4%) INTERNATIONAL 0 (0.0%) 1 (1.1%) 1 (0.4%) NORMALISED RATIO DECREASED LIVER FUNCTION TEST 1 (0.5%) 0 (0.0%) 1 (0.4%) ABNORMAL METABOLISM AND NUTRITION 3 (1.6%) 5 (5.3%) 8 (2.9%) DISORDERS ALKALOSIS 0 (0.0%) 1 (1.1%) 1 (0.4%) ANOREXIA 1 (0.5%) 0 (0.0%) 1 (0.4%) DEHYDRATION 2 (1.1%) 2 (2.1%) 4 (1.4%)

26 Percutaneous (N=184 Surgery (N=95 All Patients (N=279 DIABETIC KETOACIDOSIS 1 (0.5%) 0 (0.0%) 1 (0.4%) FLUID OVERLOAD 0 (0.0%) 1 (1.1%) 1 (0.4%) HYPONATRAEMIA 0 (0.0%) 1 (1.1%) 1 (0.4%) MALNUTRITION 0 (0.0%) 2 (2.1%) 2 (0.7%) MUSCULOSKELETAL AND 2 (1.1%) 2 (2.1%) 4 (1.4%) CONNECTIVE TISSUE DISORDERS ARTHRALGIA 1 (0.5%) 0 (0.0%) 1 (0.4%) BACK PAIN 1 (0.5%) 0 (0.0%) 1 (0.4%) MUSCULOSKELETAL CHEST 0 (0.0%) 1 (1.1%) 1 (0.4%) PAIN PAIN IN EXTREMITY 0 (0.0%) 1 (1.1%) 1 (0.4%) NEOPLASMS BENIGN, 4 (2.2%) 2 (2.1%) 6 (2.2%) MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) BASAL CELL CARCINOMA 1 (0.5%) 0 (0.0%) 1 (0.4%) BREAST CANCER 1 (0.5%) 0 (0.0%) 1 (0.4%) LUNG CANCER METASTATIC 0 (0.0%) 1 (1.1%) 1 (0.4%) MULTIPLE MYELOMA 2 (1.1%) 0 (0.0%) 2 (0.7%)

27 Percutaneous (N=184 Surgery (N=95 All Patients (N=279 NON-SMALL CELL LUNG 0 (0.0%) 1 (1.1%) 1 (0.4%) CANCER METASTATIC NERVOUS SYSTEM DISORDERS 7 (3.8%) 3 (3.2%) 10 (3.6%) CEREBRAL HAEMORRHAGE 1 (0.5%) 0 (0.0%) 1 (0.4%) CEREBROVASCULAR 2 (1.1%) 2 (2.1%) 4 (1.4%) ACCIDENT DIZZINESS 1 (0.5%) 0 (0.0%) 1 (0.4%) METABOLIC 0 (0.0%) 1 (1.1%) 1 (0.4%) ENCEPHALOPATHY SYNCOPE 2 (1.1%) 0 (0.0%) 2 (0.7%) TRANSIENT ISCHAEMIC 1 (0.5%) 0 (0.0%) 1 (0.4%) ATTACK PSYCHIATRIC DISORDERS 1 (0.5%) 0 (0.0%) 1 (0.4%) DEPRESSION 1 (0.5%) 0 (0.0%) 1 (0.4%) MENTAL STATUS CHANGES 1 (0.5%) 0 (0.0%) 1 (0.4%) RENAL AND URINARY 3 (1.6%) 3 (3.2%) 6 (2.2%) DISORDERS NEPHROPATHY TOXIC 0 (0.0%) 1 (1.1%) 1 (0.4%) RENAL FAILURE ACUTE 3 (1.6%) 1 (1.1%) 4 (1.4%) RENAL FAILURE CHRONIC 0 (0.0%) 1 (1.1%) 1 (0.4%)

28 Percutaneous (N=184 Surgery (N=95 All Patients (N=279 URINARY INCONTINENCE 0 (0.0%) 1 (1.1%) 1 (0.4%) REPRODUCTIVE SYSTEM AND 2 (1.1%) 0 (0.0%) 2 (0.7%) BREAST DISORDERS BENIGN PROSTATIC 1 (0.5%) 0 (0.0%) 1 (0.4%) HYPERPLASIA VAGINAL HAEMORRHAGE 1 (0.5%) 0 (0.0%) 1 (0.4%) RESPIRATORY, THORACIC AND 20 (10.9%) 13 (13.7%) 33 (11.8%) MEDIASTINAL DISORDERS ATELECTASIS 1 (0.5%) 1 (1.1%) 2 (0.7%) CHRONIC OBSTRUCTIVE 0 (0.0%) 1 (1.1%) 1 (0.4%) PULMONARY DISEASE DYSPNOEA EXACERBATED 1 (0.5%) 0 (0.0%) 1 (0.4%) DYSPNOEA 4 (2.2%) 0 (0.0%) 4 (1.4%) EPISTAXIS 1 (0.5%) 0 (0.0%) 1 (0.4%) HAEMOPTYSIS 1 (0.5%) 0 (0.0%) 1 (0.4%) HYPOXIA 0 (0.0%) 1 (1.1%) 1 (0.4%) LARYNGOSPASM 0 (0.0%) 1 (1.1%) 1 (0.4%) LUNG DISORDER 0 (0.0%) 1 (1.1%) 1 (0.4%) PLEURAL EFFUSION 3 (1.6%) 4 (4.2%) 7 (2.5%) PNEUMONIA ASPIRATION 0 (0.0%) 1 (1.1%) 1 (0.4%)

29 Percutaneous (N=184 Surgery (N=95 All Patients (N=279 PNEUMOTHORAX 1 (0.5%) 2 (2.1%) 3 (1.1%) PULMONARY EMBOLISM 1 (0.5%) 0 (0.0%) 1 (0.4%) PULMONARY HAEMATOMA 0 (0.0%) 1 (1.1%) 1 (0.4%) PULMONARY OEDEMA 2 (1.1%) 3 (3.2%) 5 (1.8%) RESPIRATORY DISTRESS 3 (1.6%) 0 (0.0%) 3 (1.1%) RESPIRATORY FAILURE 5 (2.7%) 5 (5.3%) 10 (3.6%) STATUS ASTHMATICUS 1 (0.5%) 0 (0.0%) 1 (0.4%) STRIDOR 0 (0.0%) 1 (1.1%) 1 (0.4%) SKIN AND SUBCUTANEOUS 1 (0.5%) 0 (0.0%) 1 (0.4%) TISSUE DISORDERS DECUBITUS ULCER 1 (0.5%) 0 (0.0%) 1 (0.4%) SURGICAL AND MEDICAL 4 (2.2%) 3 (3.2%) 7 (2.5%) PROCEDURES COLECTOMY 0 (0.0%) 1 (1.1%) 1 (0.4%) IMPLANTABLE 1 (0.5%) 1 (1.1%) 2 (0.7%) DEFIBRILLATOR INSERTION IMPLANTABLE 1 (0.5%) 0 (0.0%) 1 (0.4%) DEFIBRILLATOR REPLACEMENT MITRAL VALVE 1 (0.5%) 0 (0.0%) 1 (0.4%) REPLACEMENT

30 Percutaneous (N=184 Surgery (N=95 All Patients (N=279 PACKED RED BLOOD CELL 1 (0.5%) 0 (0.0%) 1 (0.4%) TRANSFUSION STERNAL WIRING 0 (0.0%) 1 (1.1%) 1 (0.4%) VASCULAR DISORDERS 21 (11.4%) 7 (7.4%) 28 (10.0%) AORTIC DISSECTION 1 (0.5%) 0 (0.0%) 1 (0.4%) ARTERIOVENOUS FISTULA 1 (0.5%) 0 (0.0%) 1 (0.4%) ARTERY DISSECTION 1 (0.5%) 0 (0.0%) 1 (0.4%) DEEP VEIN THROMBOSIS 5 (2.7%) 0 (0.0%) 5 (1.8%) EXTREMITY NECROSIS 0 (0.0%) 1 (1.1%) 1 (0.4%) HAEMATOMA 1 (0.5%) 0 (0.0%) 1 (0.4%) HAEMORRHAGE 3 (1.6%) 2 (2.1%) 5 (1.8%) HYPERTENSION 0 (0.0%) 1 (1.1%) 1 (0.4%) HYPOTENSION 6 (3.3%) 0 (0.0%) 6 (2.2%) JUGULAR VEIN THROMBOSIS 0 (0.0%) 1 (1.1%) 1 (0.4%) PERIPHERAL VASCULAR 1 (0.5%) 0 (0.0%) 1 (0.4%) DISORDER SHOCK HAEMORRHAGIC 0 (0.0%) 1 (1.1%) 1 (0.4%) SHOCK 1 (0.5%) 0 (0.0%) 1 (0.4%) THROMBOSIS 1 (0.5%) 1 (1.1%) 2 (0.7%)

31 Percutaneous (N=184 Surgery (N=95 All Patients (N=279 VASCULAR 3 (1.6%) 0 (0.0%) 3 (1.1%) PSEUDOANEURYSM VENOUS THROMBOSIS 0 (0.0%) 1 (1.1%) 1 (0.4%)

32 Supplementary Figure Legend Supplementary Figure 1. Patient Flow: Per-Protocol Cohort. Patients available for analysis at 30 days (safety), 12 months (efficacy) are shown. Supplementary Figure 2. Treatment by Subgroup Interactions: Intention to Treat Cohort. Major Adverse Event at 30 days. The difference in MAE rates between treatment arms (percutaneous-surgery) are displayed for all randomized patients and according to 4 post-hoc subgroups, with 95% confidence intervals.

33 Supplementary Figure 1.

34 Supplementary Figure 2