International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA)
- Conditions
- Myocardial IschemiaCardiovascular DiseasesCoronary DiseaseCoronary Artery DiseaseHeart Diseases
- Interventions
- Procedure: cardiac catheterizationBehavioral: LifestyleProcedure: coronary artery bypass graft surgeryProcedure: percutaneous coronary interventionDrug: Medication
- Registration Number
- NCT01471522
- Lead Sponsor
- NYU Langone Health
- Brief Summary
The purpose of the ISCHEMIA trial is to determine the best management strategy for higher-risk patients with stable ischemic heart disease (SIHD). This is a multicenter randomized controlled trial with 5179 randomized participants with moderate or severe ischemia on stress testing. A blinded coronary computed tomography angiogram (CCTA) was performed in most participants with eGFR ≥60 mL/min/1.73m2 to identify and exclude participants with either significant unprotected left main disease (≥50% stenosis) or those without obstructive CAD (\<50% stenosis in all major coronary arteries). Of 8518 participants enrolled, those that had insufficient ischemia, ineligible anatomy demonstrated on CCTA or another exclusion criterion, did not go on to randomization. Eligible participants were then assigned at random to a routine invasive strategy (INV) with cardiac catheterization followed by revascularization, if feasible, plus optimal medical therapy (OMT) or to a conservative strategy (CON) of OMT, with cardiac catheterization and revascularization reserved for those who fail OMT.
SPECIFIC AIMS
A. Primary Aim The primary aim of the ISCHEMIA trial is to determine whether an initial invasive strategy of cardiac catheterization followed by optimal revascularization, if feasible, in addition to OMT, will reduce the primary composite endpoint of cardiovascular death, nonfatal myocardial infarction, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure in participants with SIHD and moderate or severe ischemia over an average follow-up of approximately 3.5 years compared with an initial conservative strategy of OMT alone with catheterization reserved for failure of OMT.
B. Secondary Aims Secondary aims are to determine whether an initial invasive strategy compared to a conservative strategy will improve: 1) the composite of CV death or MI; 2) angina symptoms and quality of life, as assessed by the Seattle Angina Questionnaire; 3) all-cause mortality; 4) net clinical benefit assessed by including stroke in the primary and secondary composite endpoints; and 5) individual components of the composite endpoints.
Condition: Coronary Disease Procedure: Coronary CT Angiogram Procedure: Cardiac catheterization Phase: Phase III per NIH
Condition: Cardiovascular Diseases Procedure: Angioplasty, Transluminal, Percutaneous Coronary, other catheter-based interventions Phase: Phase III per NIH
Condition: Heart Diseases Procedure: Coronary Artery Bypass Surgery Phase: Phase III per NIH
- Detailed Description
BACKGROUND:
Evidence supporting a routine invasive practice paradigm for patients with SIHD is outdated. In strategy trials conducted in the 1970s, coronary artery bypass grafting (CABG) improved survival as compared with no CABG in SIHD patients with high-risk anatomic features. The relevance of these studies today is speculative because contemporary secondary prevention-aspirin, beta-blockers, statins, ACE inhibitors, and lifestyle interventions-were used minimally if at all. Subsequent trials have compared percutaneous coronary intervention (PCI) with medical therapy, as PCI has replaced CABG as the dominant method of revascularization for SIHD. To date, PCI has not been shown to reduce death or myocardial infarction (MI) compared with medical therapy in SIHD patients.
COURAGE and BARI 2D, the two largest trials comparing coronary revascularization vs. medical therapy in SIHD patients, found that among patients selected on the basis of coronary anatomy after cardiac catheterization, an initial management strategy of coronary revascularization (PCI, PCI or CABG, respectively) did not reduce the primary endpoints of death or MI (COURAGE), or death (BARI 2D) compared with OMT alone. These data suggest, but do not prove, that routine cardiac catheterization--which often leads to ad hoc PCI through the diagnostic-therapeutic cascade--may not be required in SIHD patients. However, most patients enrolled in COURAGE and BARI 2D who had ischemia severity documented at baseline had only mild or moderate ischemia, leaving open the question of the appropriate role of cardiac catheterization and revascularization among higher-risk patients with more severe ischemia. Observational data suggest that revascularization of patients with moderate-to-severe ischemia is associated with a lower mortality than medical therapy alone, but such data cannot establish a cause and effect relationship. In clinical practice only about half such patients are referred for cardiac catheterization, indicating equipoise. Furthermore, analysis of outcomes for 468 COURAGE patients with moderate-to-severe ischemia at baseline did not reveal a benefit from PCI. This issue cannot be resolved using available data because all prior SIHD strategy trials enrolled patients after cardiac catheterization, introducing undefined selection biases (e.g., highest risk patients not enrolled) and making translation of study results problematic for clinicians managing patients who have not yet had cardiac catheterization.
A clinical trial in SIHD patients uniformly at higher risk (which could not have been performed before COURAGE and BARI 2D results were available) is needed to inform optimal management for such patients.
DESIGN NARRATIVE, INCLUDING MODIFICATIONS DURING THE TRIAL
Primary Endpoint
A composite of CV death, MI, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure was proposed as the primary endpoint in the application that was funded by NLHBI, with a secondary endpoint of CV death or MI. Study protocol version 1.0 was finalized on January 18, 2012 after review and approval by the protocol review committee (DSMB) with the primary endpoint specified as the composite of CV death or MI. Regarding the final status of the primary endpoint, the protocol stated:
"To ensure that the primary analysis is well-powered and useful, a prospective plan to allow extending follow-up and/or changing the primary endpoint based on aggregate event rate data will be established prior to the first review of unblinded trial data. At a designated time during the trial, an analysis will be conducted to estimate the overall aggregate primary endpoint event rate and project the final number of observed events. If the estimated unconditional power (i.e. based on aggregate event rate data; not by treatment group) is less than the originally targeted 90%, then one or more of the following options will be considered:
1. Extend follow-up to allow more events to accrue.
2. Change the primary endpoint to one that occurs more frequently. The current primary endpoint would become a secondary endpoint. The proposed new primary endpoint would be the composite of CV death, MI, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure.
3. Follow the recommendation of an independent advisory panel. An independent advisory panel, separate from the DSMB, will be convened for the purpose of reviewing unconditional power estimates and making a recommendation to the NHLBI Director. Members of this panel will not have access to unblinded data by treatment group or other data that may bias their recommendation." All 5 event types were adjudicated throughout the trial. Study protocol v2.0 (January 2014) allowed ischemia eligibility by non-imaging exercise stress test if more stringent (≥70% stenosis) CCTA criteria were met. The 2016 protocol addendum describes the NHLBI-approved reduction in sample size and extension of recruitment and follow-up due to slower than projected recruitment.
The pre-specified first analysis for monitoring and projecting the final aggregate number of primary endpoint events was conducted in 2015. In 2016, the projected need to increase the power by extending follow-up and elevating the 5-component secondary endpoint to become primary was discussed at Steering Committee and Investigator meetings and communicated by email.
An Independent Advisory Panel convened by NHLBI met in May 2017, and in June 2017 NHLBI approved the Independent Advisory Panel's recommendation to elevate the 5-component secondary endpoint to become primary and retain the 2-component composite as a key secondary endpoint. The panel also recommended extension of follow-up. This was communicated to the Steering Committee and Investigators at August and November 2017 meetings and by email. The last visit date was June 30, 2019.
A statistical plan developed for the Independent Advisory Panel process in 2012 specified that a decision about changing the primary endpoint would be targeted to occur before 75% of the final number of primary endpoint events had accrued. Although the final number of primary endpoint events was unknown during the course of the trial, estimates performed at the time of the Advisory Panel meeting suggested that the ratio of accrued endpoint events to final endpoint events was below 50%. See Maron DJ et al. Am Heart J. 2018 201:124-135. PMC6005768 for additional details about modifications to the trial while it was being conducted.
Analysis of Patients' Health Status as a Key Secondary Endpoint
A key secondary objective of the ISCHEMIA trial is to compare the quality of life outcomes-patients' symptoms, functioning and well-being-between those assigned to an invasive strategy as compared with a conservative strategy. In the protocol, angina frequency and disease-specific quality of life measured by the Seattle Angina Questionnaire (SAQ) Angina Frequency and Quality of Life scales, respectively, are described as the tools that will be used to make this comparative assessment. Recent work has indicated that it is possible to combine the information from the individual domain scores in the SAQ into a new Summary Score that captures the information from the SAQ Angina Frequency, Physical Limitation and Quality of Life scales into a single overall score. The advantages of using a summary score as the primary measure of QOL effects of a therapy are a single primary endpoint comparison rather than two or three (eliminating concerns some may have about multiple comparisons) and a more intuitive holistic (patient-centric) interpretation of the effectiveness results. With these advantages in mind, the ISCHEMIA leadership has agreed that the SAQ Summary Score will be designated as the primary way this outcome for this key secondary endpoint of the ISCHEMIA trial will be analyzed and interpreted, with the individual SAQ scores being used in a secondary, explanatory and descriptive role.
PARTICIPATING COUNTRIES:
North America:
Canada; Mexico; USA
South America:
Argentina; Brazil; Peru
Asia:
China; India; Japan; Malaysia; Singapore; Taiwan; Thailand; Russian Federation
Pacifica:
Australia; New Zealand
Europe:
Austria; Belgium; France; Germany; Hungary; Italy; Lithuania; Macedonia; Netherlands; Poland; Portugal; Romania; Serbia; Spain; Sweden; Switzerland; UK
Middle East:
Egypt; Israel; Saudi Arabia
Africa:
South Africa
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 5179
- At least moderate ischemia on a qualifying stress test
- Participant is willing to comply with all aspects of the protocol, including adherence to the assigned strategy, medical therapy and follow-up visits
- Participant is willing to give written informed consent
- Age ≥ 21 years
- LVEF < 35%
- History of unprotected left main stenosis >50% on prior coronary computed tomography angiography (CCTA) or prior cardiac catheterization (if available)
- Finding of "no obstructive CAD" (<50% stenosis in all major epicardial vessels) on prior CCTA or prior catheterization, performed within 12 months
- Coronary anatomy unsuitable for either PCI or CABG
- Unacceptable level of angina despite maximal medical therapy
- Very dissatisfied with medical management of angina
- History of noncompliance with medical therapy
- Acute coronary syndrome within the previous 2 months
- PCI within the previous 12 months
- Stroke within the previous 6 months or spontaneous intracranial hemorrhage at any time
- History of ventricular tachycardia requiring therapy for termination, or symptomatic sustained ventricular tachycardia not due to a transient reversible cause
- NYHA class III-IV heart failure at entry or hospitalization for exacerbation of chronic heart failure within the previous 6 months
- Non-ischemic dilated or hypertrophic cardiomyopathy
- End stage renal disease on dialysis or estimated glomerular filtration rate (eGFR) <30mL/min (not an exclusion criterion for CKD ancillary trial, see CKD ancillary trial, Section 18)
- Severe valvular disease or valvular disease likely to require surgery or percutaneous valve replacement during the trial
- Allergy to radiographic contrast that cannot be adequately pre-medicated, or any prior anaphylaxis to radiographic contrast
- Planned major surgery necessitating interruption of dual antiplatelet therapy (note that patients may be eligible after planned surgery)
- Life expectancy less than the duration of the trial due to non-cardiovascular comorbidity
- Pregnancy (known to be pregnant; to be confirmed before CCTA and/or randomization, if applicable)
- Patient who, in the judgment of the patient's physician, is likely to have significant unprotected left main stenosis (Those who are able to undergo CCTA will have visual assessment of the left main coronary artery by the CCTA core lab)
- Enrolled in a competing trial that involves a non-approved cardiac drug or device
- Inability to comply with the protocol
- Exceeds the weight or size limit for CCTA or cardiac catheterization at the site
- Canadian Cardiovascular Society Class III angina of recent onset, OR angina of any class with a rapidly progressive or accelerating pattern
- Canadian Cardiovascular Society Class IV angina, including unprovoked rest angina
- High risk of bleeding which would contraindicate the use of dual antiplatelet therapy
- Cardiac transplant recipient
- Prior CABG, unless CABG was performed more than 12 months ago, and coronary anatomy has been demonstrated to be suitable for PCI or repeat CABG to accomplish complete revascularization of ischemic areas (CCC approval required)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Invasive Strategy (INV) Medication Routine invasive strategy with cardiac catheterization followed by revascularization plus optimal medical therapy. Invasive Strategy (INV) cardiac catheterization Routine invasive strategy with cardiac catheterization followed by revascularization plus optimal medical therapy. Conservative Strategy Lifestyle Optimal medical therapy with cardiac catheterization and revascularization reserved for patients with acute coronary syndrome, ischemic heart failure, resuscitated cardiac arrest or refractory symptoms. Conservative Strategy Medication Optimal medical therapy with cardiac catheterization and revascularization reserved for patients with acute coronary syndrome, ischemic heart failure, resuscitated cardiac arrest or refractory symptoms. Invasive Strategy (INV) coronary artery bypass graft surgery Routine invasive strategy with cardiac catheterization followed by revascularization plus optimal medical therapy. Invasive Strategy (INV) percutaneous coronary intervention Routine invasive strategy with cardiac catheterization followed by revascularization plus optimal medical therapy. Invasive Strategy (INV) Lifestyle Routine invasive strategy with cardiac catheterization followed by revascularization plus optimal medical therapy.
- Primary Outcome Measures
Name Time Method Estimated Difference in Cumulative Event Rate of Myocardial Infarction: Invasive Minus Conservative 5 years Cumulative Event Rate of Primary Composite Outcome (Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, Heart Failure, or Resuscitated Cardiac Arrest) 5 years This measure represents the estimated cumulative probability of experiencing the primary endpoint within the indicated timeframe in each treatment group. The interpretation of the measure is similar to Kaplan-Meier event rates. Estimates are expressed as percentages ranging from 0% (endpoint is certain not to occur) to 100% (endpoint is certain to occur).
Cumulative Event Rate of Death From Cardiovascular Causes or Myocardial Infarction 5 years This measure represents the estimated cumulative probability of experiencing Death from cardiovascular causes or myocardial infarction within the indicated timeframe in each treatment group. The interpretation of the measure is similar to Kaplan-Meier event rates. Estimates are expressed as percentages ranging from 0% (endpoint is certain not to occur) to 100% (endpoint is certain to occur).
Number of Participants That Experienced Death From Any Cause 5 years Number of Participants That Experienced Myocardial Infarction 5 years Cumulative Event Rate of Myocardial Infarction 5 years Estimated Difference in Cumulative Event Rate ( %) of Primary Composite Outcome: Invasive Minus Conservative 5 years The primary composite outcome includes death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest.
Estimated Difference in Cumulative Event Rate of Death From Any Cause: Invasive Minus Conservative 5 years Number of Participants That Experienced Death From Cardiovascular Causes or Myocardial Infarction 5 years Cumulative Event Rate of Death From Any Cause 5 years Primary Composite Outcome: Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, Heart Failure, or Resuscitated Cardiac Arrest 3.2 year follow-up (median) Estimated Difference in Cumulative Event Rate of Death From Cardiovascular Causes: Invasive Minus Conservative or Myocardial Infarction Between Invasive and Conservative Strategies 5 years
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (320)
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
VA Palo Alto HealthCare System
🇺🇸Palo Alto, California, United States
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
South Denver Cardiology Associates, P.C.
🇺🇸Littleton, Colorado, United States
Stanford University School of Medicine
🇺🇸Stanford, California, United States
NYU Langone Medical Center-Bellevue Hospital
🇺🇸New York, New York, United States
Capital Cardiology Associates
🇺🇸Albany, New York, United States
Kaiser Permanente San Jose
🇺🇸San Jose, California, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
University of California Irvine Medical Center
🇺🇸Orange, California, United States
Cardiovascular Center of Sarasota
🇺🇸Sarasota, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Medical Center of the Rockies
🇺🇸Loveland, Colorado, United States
Torrance Memorial Medical Center
🇺🇸Torrance, California, United States
Samuel Stratton VA Medical Center of Albany NY
🇺🇸Albany, New York, United States
Yuma Regional Medical Center
🇺🇸Yuma, Arizona, United States
Karolinska Institutet at Danderyd Hospital
🇸🇪Stockholm, Sweden
Malcom Randall VAMC
🇺🇸Gainesville, Florida, United States
NYU-HHC Lincoln Medical and Mental Health Center
🇺🇸Bronx, New York, United States
Midwest Cardiovascular Research Foundation
🇺🇸Davenport, Iowa, United States
Daytona Heart Group
🇺🇸Daytona Beach, Florida, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Sarasota Memorial Hospital
🇺🇸Sarasota, Florida, United States
Advanced Heart Care Group
🇺🇸Fairview Heights, Illinois, United States
Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
VA New York Harbor Health Care System
🇺🇸New York, New York, United States
Albany Medical Center Hospital
🇺🇸Albany, New York, United States
New York University - Langone Cardiovascular Associates
🇺🇸Flushing, New York, United States
New York -Presbyterian/Brooklyn Methodist Hospital
🇺🇸Brooklyn, New York, United States
Michigan Heart, PC
🇺🇸Ypsilanti, Michigan, United States
Cardiology Associates of Schenectady P.C.
🇺🇸Schenectady, New York, United States
NYP Medical Medical Group Hudson Valley Cardiology
🇺🇸Cortlandt Manor, New York, United States
NYU Winthrop
🇺🇸Mineola, New York, United States
NYU-HHC Woodhull Hospital
🇺🇸Brooklyn, New York, United States
Hospital da Bahia
🇧🇷Salvador, Brazil
Oklahoma Heart Institute
🇺🇸Tulsa, Oklahoma, United States
Asheville Cardiology Associates
🇺🇸Asheville, North Carolina, United States
Conemaugh Valley Memorial Hospital
🇺🇸Johnstown, Pennsylvania, United States
Heart Institute (InCor) University of São Paulo
🇧🇷Sao Paulo, Brazil
Dixie Medical Group
🇨🇦Mississauga, Ontario, Canada
Luton and Dunstable University Hospital NHS FT
🇬🇧Luton, Berdfordshire, United Kingdom
Bedford Hospital NHS Trust
🇬🇧Bedford, Bedfordshire, United Kingdom
Hospital La Paz. IdiPaz
🇪🇸Madrid, Spain
HUVA, Hospital Clínico Universitario Virgen De La Arrixaca
🇪🇸Murcia, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Uppsala University
🇸🇪Uppsala, Sweden
The James Cook University Hospital, Middlesbrough
🇬🇧Middlesbrough, Cleveland, United Kingdom
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Universitario y Politecnico La Fe
🇪🇸Valencia, Spain
Nottingham University Hospitals
🇬🇧Nottingham, Notts, United Kingdom
Russells Hall Hospital
🇬🇧Dudley, West Midlands, United Kingdom
Northwick Park Hospital Harrow/ Royal Brompton Hospital London
🇬🇧Harrow, Middlesex, United Kingdom
Bradford Royal Infirmary
🇬🇧Bradford, West Yorkshire, United Kingdom
University College London Hospitals NHS Foundation Trust/Barts Health NHS Trust
🇬🇧London, United Kingdom
Brigham & Women's Hospital, Harvard Medical School
🇺🇸Boston, Massachusetts, United States
Louis Stokes Cleveland Veterans Affairs Medical Center
🇺🇸Cleveland, Ohio, United States
Women's College Hospital
🇨🇦Toronto, Ontario, Canada
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Baylor St. Luke's Medical Center
🇺🇸Houston, Texas, United States
Houston Heart & Vascular Associates
🇺🇸Houston, Texas, United States
Clínica Privada Vélez Sarsfield
🇦🇷Cordoba, Argentina
John Hunter Hospital
🇦🇺New Lambton Heights, New South Wales, Australia
Flinders Medical Centre
🇦🇺Adelaide, South Australia, Australia
UCSF - Fresno Community Regional Medical Center
🇺🇸Fresno, California, United States
Palo Alto Medical Foundation Research Institute
🇺🇸Palo Alto, California, United States
Coastal Heart Medical Group
🇺🇸Santa Ana, California, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
VA Boston Healthcare System
🇺🇸West Roxbury, Massachusetts, United States
Saint Vincent Hospital at Worcester Medical Center
🇺🇸Worcester, Massachusetts, United States
The Queen Elizabeth Hospital
🇦🇺Woodville South, South Australia, Australia
HealthEast Saint Joseph's Hospital
🇺🇸Saint Paul, Minnesota, United States
AtlantiCare Regional Medical Center
🇺🇸Pomona, New Jersey, United States
Northwell Health - Manhasset
🇺🇸Manhasset, New York, United States
Mid Valley Cardiology
🇺🇸Kingston, New York, United States
Beth Israel Medical Center
🇺🇸New York, New York, United States
NYU New York Medical Associates
🇺🇸New York, New York, United States
Ohio Health Grant Medical Center
🇺🇸Columbus, Ohio, United States
Saint Luke's Hospital and Health Network
🇺🇸Bethlehem, Pennsylvania, United States
Miriam Hospital
🇺🇸Providence, Rhode Island, United States
Kent Hospital
🇺🇸Warwick, Rhode Island, United States
V.A. North Texas Health Care System
🇺🇸Dallas, Texas, United States
Baylor Research Institute at Legacy Heart Center
🇺🇸Plano, Texas, United States
The Heart Hospital Baylor
🇺🇸Plano, Texas, United States
Medicus Alliance Clinical Research Org., Inc.
🇺🇸Sugar Land, Texas, United States
Wichita Falls Heart Clinic
🇺🇸Wichita Falls, Texas, United States
Cardiovascular Associates, Ltd.
🇺🇸Chesapeake, Virginia, United States
Stroobants Cardiovascular Center
🇺🇸Lynchburg, Virginia, United States
Winchester Cardiology and Vascular Medicine, PC
🇺🇸Winchester, Virginia, United States
University of Washington Medical Center
🇺🇸Bellevue, Washington, United States
Gundersen Lutheran Medical Center
🇺🇸La Crosse, Wisconsin, United States
Clinica Romagosa and Clinica De La Familia
🇦🇷Cordoba, Argentina
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
LKH Graz West Austria
🇦🇹Graz, Stmk, Austria
Medical University of Vienna, Department of Cardiology
🇦🇹Vienna, Wien, Austria
Wilhelminen Hospital Vienna
🇦🇹Vienna, Wien, Austria
University Hospital Leuven
🇧🇪Leuven, Brabant, Belgium
Fundacao Bahiana de Cardilogia
🇧🇷Salvador, Bahia, Brazil
Quanta Diagnostico & Terapia
🇧🇷Curitiba, Parana, Brazil
Hospital Cardiologico Costantini
🇧🇷Curitiba, Parana, Brazil
Hospital de Clinicas de Porto Alegre
🇧🇷Porto Alegre, RS, Brazil
Hospital Sao Vicente de Paulo
🇧🇷Fundo, RS, Brazil
Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
🇧🇷Ribeirao Preto, Sao Paulo, Brazil
Hospital TotalCor
🇧🇷Sao Paulo, SP, Brazil
Unifesp - Hospital Sao Paulo
🇧🇷Sao Paulo, Brazil
Hospital Celso Pierro
🇧🇷Sao Paulo, Brazil
University of Alberta
🇨🇦Edmonton, Alberta, Canada
Hamilton General Hospital
🇨🇦Hamilton, Ontario, Canada
West Lincoln Memorial Hospital
🇨🇦Grimsby, Ontario, Canada
Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Dr. James Cha
🇨🇦Oshawa, Ontario, Canada
Scarborough Cardiology Research
🇨🇦Scarborough, Ontario, Canada
Saint Catharines General Hospital
🇨🇦St. Catharines, Ontario, Canada
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
University Health Network
🇨🇦Toronto, Ontario, Canada
Northwest GTA Cardiovascular and Heart Rhythm Program
🇨🇦Vaughan, Ontario, Canada
Montreal Heart Institute
🇨🇦Montreal, Quebec, Canada
Centre Intégré Universitaire de Santé et de Services Sociaux du Montréal
🇨🇦Montréal, Quebec, Canada
CISSSL - Hopital Pierre-Le Gardeur
🇨🇦Terrebonne, Quebec, Canada
Centre Hospitalier de Regional Trois-Rivieres
🇨🇦Trois-Rivieres, Quebec, Canada
University of Ottawa Heart Institute
🇨🇦Ottawa, Canada
Liangxiang Hospital, Beijing Fangshan District
🇨🇳Beijing, Fangshan, China
Guangdong General Hospital
🇨🇳Guangzhou, Guangdong, China
The Second Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Tongji Medical College
🇨🇳Wuhan, Hubei, China
Affiliated Hospital of Jining Medical University
🇨🇳Jining, Shandong, China
Qingdao Fuwai Hospital
🇨🇳Qingdao, Shandong, China
Shanxi Cardiovascular Hospital
🇨🇳Taiyuan, Shanxi, China
Shanxi Provincial People's Hospital
🇨🇳Xian, Shanxi, China
TEDA International Cardiovascular Hospital
🇨🇳Tianjing, Tianjing, China
Cairo University
🇪🇬Cairo, Egypt
C.H. Louis Pasteur
🇫🇷Chatres, Centre, France
Ambroise Pare Hospital
🇫🇷Boulogne, Ile De France, France
Antoine-Beclere Hospital
🇫🇷Clamart Cedex, Ile-de-France, France
Bichat Hospital
🇫🇷Paris, Ile-de-France, France
Grenoble University Hospital
🇫🇷Grenoble, Isere, France
Centre Hospitalier Universitaire d'Angers
🇫🇷Angers Cedex 9, Pays De La Loire, France
Robert-Bosch-Krankenhaus
🇩🇪Stuttgart, BW, Germany
Universitatsklinikum Bonn
🇩🇪Bonn, NRW, Germany
Praxisklinik Herz Und Gefaesse
🇩🇪Dresden, Saxony, Germany
University Hospital Jena
🇩🇪Jena, Thuringia, Germany
University of Szeged
🇭🇺Szeged, Szeged Megyei Varos, Hungary
Military Hospital, Budapest
🇭🇺Budapest, Hungary
Heart and Vascular Center, Semmelweis University
🇭🇺Budapest, Hungary
George Gottsegen National Institute of Cardiology
🇭🇺Budapest, Hungary
CARE Hospital
🇮🇳Hyderabad, Andhra Pradesh, India
Gurunanak CARE Hospital
🇮🇳Hyderabad, AP, India
Batra Hospital and Medical Research Centre (BHMRC)
🇮🇳New Delhi, Delhi, India
Sri Jayadeva Institute of Cardiovascular Sciences and Research
🇮🇳Bangalore, Karnataka, India
MOSC Medical College Hospital, Kolenchery
🇮🇳Kolenchery, Kerala, India
Sree Chitra Tirunal Institute for Medical Sciences and Technology
🇮🇳Trivandrum, Kerala, India
Ruby Hall Clinic,Grant Medical Foundation
🇮🇳Pune, Maharashtra, India
KEM Hospital Pune
🇮🇳Pune, Maharashtra, India
Hero DMC Heart Institute, Dayanand Medical College and Hospital
🇮🇳Ludhiana, Punjab, India
CARE Nampally
🇮🇳Hyderabad, Telangana, India
Apollo Research & Innovations
🇮🇳Hyderabad, Telangana, India
King George's Medical University, Department of Cardiology
🇮🇳Lucknow, Uttar Pradesh, India
All India Institute of Medical Sciences
🇮🇳New Delhi, India
Assuta Medical Centers
🇮🇱Tel-Aviv, Israel
Cardiology and CCU - Ospedali Riuniti Ancona
🇮🇹Ancona, Marche, Italy
Azienda Servizi Sanitaria n.3 Alto Friuli-Collinare-Medio Friuli
🇮🇹Tolmezzo, Udine, Italy
National Cerebral and Cardiovascular Center
🇯🇵Suita-shi, Osaka, Japan
Saitama Medical University
🇯🇵Hidaka, Saitama, Japan
Vilnius University Hospital Santariskes Clinic
🇱🇹Vilnius, Lithuania
Instituto Nacional de Cardiología "Ignacio Chávez"
🇲🇽Mexico City, Distrito Federal, Mexico
Instituto Mexicano del Seguro Social
🇲🇽Benito Juarez, DF, Mexico
Waikato Hospital
🇳🇿Hamilton, Waikato, New Zealand
Isala Klinieken
🇳🇱Zwolle, Netherlands
Radboudumc
🇳🇱Nijmegen, Netherlands
Auckland City Hospital
🇳🇿Auckland, New Zealand
University Clinic of Cardiology
🇲🇰Skopje, Republic Of Macedo, North Macedonia
T.Marciniak Hospital
🇵🇱Wrocław, Dolny Śląsk, Poland
Cardiology Clinic, Medical University in Lodz
🇵🇱Lodz, Lodzkie, Poland
Department of Coronary Disease, John Paul II Hospital, Jagiellonian University Medical College
🇵🇱Krakow, Maopolskie, Poland
Institute of Cardiology, Warsaw
🇵🇱Warsaw, Mazovian, Poland
Coronary and Structural Heart Diseases Department, Institute of Cardiology
🇵🇱Warsaw, Mazowieckie, Poland
Medical University of Warsaw
🇵🇱Warsaw, Mazowieckie, Poland
Department of Internal Medicine and Cardiology, Infant Jesus Teaching Hospital, Medical University of Warsaw
🇵🇱Warszawa, Mazowieckie, Poland
University Hospital in Bialystok
🇵🇱Bialystok, Podlaskie, Poland
Szpital Kliniczny Przemienienia Pańskiego
🇵🇱Poznan, Poland
Medical University of Silesia, School of Medicine with the Division of Dentistry, Department of Cardiology, Congenital Heart Diseases and Electrotherapy, Silesian Center for Heart Diseases
🇵🇱Zabrze, Wojewodztwo Slaskie, Poland
Military Hospital / Medical University
🇵🇱Wroclaw, Poland
Hospital de Santa Marta
🇵🇹Lisboa, Portugal
Santa Maria University Hospital, Cardiology Department, CHLN
🇵🇹Lisbon, Portugal
Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE
🇵🇹Vila Nova de Gaia, Portugal
Emergency Institute of Cardiovascular Diseases ''Prof. Dr. C. C. Iliescu''
🇷🇴Bucharest, Romania
Emergency County Hospital Baia Mare
🇷🇴Baia Mare, Romania
National Medical Research Center for Cardiovascuar Surgery
🇷🇺Moscow, Gorod Moskva, Russian Federation
E.Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation
🇷🇺Novosibirsk, Novosibirskaya Oblast, Russian Federation
North-Western State Medical University
🇷🇺Saint Petersburg, Russian Federation
Federal Almazov North-West Medical Research Centre
🇷🇺Saint-Petersburg, Russian Federation
Clinical Center of Serbia
🇷🇸Belgrade, Serbia
University Clinical Hospital Zvezdara
🇷🇸Belgrade, Serbia
Faculty of Medicine, University of Belgrade; Cardiology Clinic, Clinical Center of Serbia
🇷🇸Belgrade, Serbia
University Hospital Center Bezanijska Kosa
🇷🇸Belgrade, Serbia
Clinical Center Kragujevac
🇷🇸Kragujevac, Serbia
Minneapolis VAMC
🇺🇸Minneapolis, Minnesota, United States
Clinic for Cardiovascular Diseases, Clinical Center Nis
🇷🇸Nis, Serbia
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Audie Murphy V.A.
🇺🇸San Antonio, Texas, United States
National University Heart Center Singapore
🇸🇬Singapore, Singapore
National Heart Centre Singapore
🇸🇬Singapore, Singapore
Tan Tock Seng Hospital
🇸🇬Singapore, Singapore
Groote Schuur Hospital / University of Cape Town
🇿🇦Cape Town, Western Cape, South Africa
Hospital Clinico Universitario de Santiago
🇪🇸Santiago de Compostela, La Coruna, Spain
Complexo Hospitalario Universitario A Coruña (CHUAC) Sergas, Department of Cardiology. INIBIC A Coruña. CIBER-CV. Universidad de A Coruña, Spain
🇪🇸A Coruna, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital De Bellvitge
🇪🇸Barcelona, Spain
Beijing Anzhen Hospital
🇨🇳Beijing, Chaoyang, China
Beijing Chao-yang Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
Chinese Academy of Medical Sciences, Fuwai Hospital
🇨🇳Beijing, Beijing, China
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
Tangshan Gongren Hospital
🇨🇳Tangshan, Hebei, China
Affiliated Zhongshan Hospital of Dalian University
🇨🇳Dalian, Liaoning, China
First Affiliated Hospital of Xinjiang Medical University
🇨🇳Urumqi, Xinjiang, China
Wuhan Asia Heart Hospital
🇨🇳Wuhan, Hubei, China
The Second Affiliated Hospital Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER)
🇮🇳Pondicherry, Tamil Nadu, India
Apollo Research and Innovation
🇮🇳Chennai, Tamil Nadu, India
Hospital Maternidade e Pronto Socorro Santa Lucia
🇧🇷Pocos de Caldas, Minas Gerais, Brazil
Hospital Lifecenter
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Dr Ram Manohar Lohia Hospital
🇮🇳New Delhi, Delhi, India
Broomfield Hospital
🇬🇧Chelmsford, Essex, United Kingdom
Sanford Health
🇺🇸Fargo, North Dakota, United States
Fortis Escort Heart Institute
🇮🇳New Delhi, Delhi, India
Fortis Healthcare Fl.t Lt. Rajan Dhall Hospital
🇮🇳New Delhi, Delhi, India
Southend University Hospital
🇬🇧Westcliff-on-Sea, Essex, United Kingdom
Hospital Pró-Cardíaco
🇧🇷Botafogo, Rio De Janeiro, Brazil
Instituto de Cardiologia de Porto Alegre
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital Sao Lucas da Pontificia Universidade Catolica do Rio Grande do Sol
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Englewood Hospital and Medical Center
🇺🇸Englewood, New Jersey, United States
University of Rochester
🇺🇸Rochester, New York, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Salt Lake City VA Medical Center
🇺🇸Salt Lake City, Utah, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
UAB Vascular Biology and Hypertension Program
🇺🇸Birmingham, Alabama, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Providence Heart and Vascular Institute
🇺🇸Portland, Oregon, United States
Ospedale "G.B. Morgagni - L. Pierantoni" Forli (AUSL della Romagna)
🇮🇹Forli, Emilia-Romagna, Italy
IRCCS "Casa Sollievo della Sofferenza"
🇮🇹San Giovanni Rotondo, FG, Italy
Policlinico di Monza, Monza MB
🇮🇹Monza, MB, Italy
AORN Dei Colli "V. Monaldi" UOC Cardiologia Università della Campania "L.Vanvitelli"
🇮🇹Napoli, Campania, Italy
Humanitas Research Hospital, Rozzano (MI)
🇮🇹Rozzano, Milano, Italy
Azienda Ospedaliera S. Croce e Carle
🇮🇹Cuneo, Piemonte, Italy
Ospedale Regionale Umberto Parini
🇮🇹Aosta, Italy
Clinica Mediterranea
🇮🇹Naples, Italy
Ospedale di Circolo e Fondazione Macchi
🇮🇹Varese, Italy
Hackensack University Medical Center
🇺🇸Saddle Brook, New Jersey, United States
Eszszk- Szent Istvan Hospital
🇭🇺Budapest, Hungary
Cardiovascular Specialists of Southwest Louisiana
🇺🇸Lake Charles, Louisiana, United States
Jacobi Medical Center
🇺🇸Bronx, New York, United States
Hospital Italiano Regional del Sur Bahia Blanca
🇦🇷Bahia Blanca, Buenos Aires, Argentina
Fundacion Favaloro
🇦🇷Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Instituto Medico DAMIC
🇦🇷Cordoba, CBA, Argentina
VAMC-White River Junction
🇺🇸White River Junction, Vermont, United States
Government Medical College
🇮🇳Calicut, Kerala, India
UO Cardiologia Ospedale SS Cosma e Damiano
🇮🇹Pescia, Tuscany, Italy
Cedars Sinai Medical Center
🇺🇸Beverly Hills, California, United States
VA Connecticut Healthcare System
🇺🇸West Haven, Connecticut, United States
Clinica Del Prado
🇦🇷Cordoba, Argentina
University of Padua- Cardiology Clinic
🇮🇹Padua, Veneto, Italy
Cardio Research Hartcentrum OLVG
🇳🇱Amsterdam, NH, Netherlands
Saint Thomas Hospital
🇺🇸Nashville, Tennessee, United States
Cardiovascular Research Unit, Craigavon Area Hospital
🇬🇧Craigavon, Northern Ireland, United Kingdom
Blackpool Teaching Hospitals
🇬🇧Blackpool, Lancashire, United Kingdom
Rambam Medical Center
🇮🇱Haifa, Israel
Instituto Neuro Cardiovascular De Las Americas
🇵🇪Miraflores, Lima, Peru
Department of Interventional Cardiology & Angiology, Institute of Cardiology
🇵🇱Warsaw, Mazowieckie, Poland
Mackay Memorial Hospital
🇨🇳Taipei City, Taiwan
Dorset County Hospital
🇬🇧Dorchester, Dorset, United Kingdom
Hampshire Hospitals NHS Foundation Trust
🇬🇧Basingstoke, Hampshire, United Kingdom
The Pennine Acute Hospitals NHS Trust
🇬🇧Oldham, Lancashire, United Kingdom
University of Calgary
🇨🇦Calgary, Alberta, Canada
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Belfast Trust
🇬🇧Belfast, Antrim, United Kingdom
Keio University Hospital
🇯🇵Shinjuku-Ku, Tokyo, Japan
Institut Jantung Negara
🇲🇾Kuala Lumpur, Wilayah Persekutuan, Malaysia
Institute of Cardiovascular Diseases Vojvodina, Sremska Kamenica, Serbia and Faculty of Medicine, University of Novi Sad
🇷🇸Sremska Kamenica, Vojvodina, Serbia
King AbdulAziz Cardiac Center
🇸🇦Riyadh, Central Province, Saudi Arabia
Ramathibodi Hospital
🇹🇭Bangkok, Thailand
Papworth Hospital
🇬🇧Cambridge, Cambridgeshire, United Kingdom
Cardiocentro
🇨🇭Lugano, Ticino, Switzerland
Royal Bournemouth Hospital
🇬🇧Bournemouth, Dorset, United Kingdom
Maharaj Nakorn Chiang Mai Hospital
🇹🇭Chiang Mai, Meung, Thailand
South Eastern Health and Social Care
🇬🇧Belfast, Northern Ireland, United Kingdom
Royal Infirmary of Edinburgh
🇬🇧Edinburgh, Scotland, United Kingdom
Centre Hospitalier Sud Francilien
🇫🇷Corbeil-Essonnes cedex, Ile De France, France
Peterborough City Hospital
🇬🇧Peterborough, Cambs, United Kingdom
The University of Hull/Castle Hill Hospital
🇬🇧Cottingham, East Yorkshire, United Kingdom
University of Glasgow
🇬🇧Clydebank, Strathclyde, United Kingdom
Pinderfields Hospital
🇬🇧Wakefield, West Yorkshire, United Kingdom
King's College NHS Foundation Hospital
🇬🇧London, United Kingdom
Central Manchester University Hospital
🇬🇧Manchester, United Kingdom
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Instituto Dante Pazzanese de Cardiologia
🇧🇷Ibirapuera, Sao Paulo, Brazil
Coney Island Hospital
🇺🇸Brooklyn, New York, United States
Mount Sinai Saint Luke's Hospital
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Indiana University/Krannert Institute of Cardiology
🇺🇸Indianapolis, Indiana, United States
Lexington VA Medical Center
🇺🇸Lexington, Kentucky, United States
Atlanta VA Medical Center
🇺🇸Decatur, Georgia, United States
Providence - Providence Park Hospital
🇺🇸Southfield, Michigan, United States
Covenant Medical Center, Inc.
🇺🇸Saginaw, Michigan, United States
Cincinnati VA Medical Center
🇺🇸Cincinnati, Ohio, United States
Holy Spirit Hospital Cardiovascular Institute
🇺🇸Camp Hill, Pennsylvania, United States
Doylestown Health Cardiology
🇺🇸Doylestown, Pennsylvania, United States
Wuhan Union Hospital, Tongji Medical College, Huazhong Science and Tech University
🇨🇳Wuhan, Hubei, China
University of South Florida
🇺🇸Tampa, Florida, United States
NIH Heart Center at Suburban Hospital
🇺🇸Bethesda, Maryland, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
NYU-HHC Kings County Hospital Center
🇺🇸Brooklyn, New York, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
Saint Luke's Hospital
🇺🇸Kansas City, Missouri, United States
Kansas City VA Medical Center
🇺🇸Kansas City, Missouri, United States
Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
Royal Free London NHS Foundation Trust
🇬🇧London, United Kingdom