OMB No. 0925-0001 and 0925-0002 (Rev. 09/17 Approved Through 03/31/2020)

BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FIVE PAGES.

NAME: Stephen Fremes MD FRCSCeRA COMMONS USER NAME (credential, e.g., agency login): SFREMESPOSITION TITLE: Cardiovascular Surgeon; Professor, University of Toronto
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing,include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)
INSTITUTION AND LOCATION

University of Toronto, Toronto, Ontario
University of Toronto, Toronto, Ontario
University of Toronto, Toronto, Ontario
University of Toronto, Toronto, Ontario
University of Toronto, Toronto, Ontario
University of Toronto, Toronto, Ontario
A.

DEGREE(if applicable)

Completion Date
MM/YYYY

BSc
MDMSc
FRCSC
FRCSC
Fellowship

05/1975
06/1979
07/1984
06/1986
06/1988
06/1989

FIELD OF STUDY

Arts & Sciences
Medicine
Medical Science
General Surgery
CVT Surgery
Cardiac Surgery

Personal Statement

I am a Staff Cardiac Surgeon at Sunnybrook HSC since 1989, a Professor of Surgery at the University ofToronto since 2001, and the inaugural Bernard Goldman Chair in Cardiovascular Surgery, with appointments
at UofT in the School of Graduate Studies, Institute of Medical Science, and the Institute of Health Policy
Management and Evaluation. I have had peer reviewed grant support for studies in cardiac surgery as aprincipal applicant or co-principal applicant for more than 30 years and have published more than 450
manuscripts in peer-reviewed journals including many in the highest impact medical journals such as N Engl J
Med, Lancet, JAMA, JACC, EHJ and Circulation, with a Google Scholar h-index of 71. My program of research
has focused on three main themes: 1) improving outcomes following CABG, 2) myocardial
protection/cardiopulmonary bypass management, and 3) transcatheter aortic valve surgery. I have utilized avariety of methodologies in my research including multicenter clinical trials, observational studies (single centerand health systems research), systematic reviews and meta-analyses, and health economics and modelling. I
have also had extensive experience with Clinical Practice Guidelines including the 2021 2021 ACC/AHA/SCAI
Guideline for Coronary Artery Revascularization. I am the NPI of the Canadian Institutes of Health Research(CIHR) funded international multi-centre Randomized comparison of the clinical Outcome of single versus
Multiple Arterial grafts trial (ROMA NCT03217006) and Co-A of the NIH-funded ROMA-QOL and (ROMA:Cog)sub-studies. As the NPI of the CIHR funded ROMA trial and the Canadian lead for the ROMA: Women GCRFF
application, I am uniquely qualified to be a MPI of the ROMA: Women NIH application.
Desai ND, Cohen EA, Naylor CD, Fremes SE; Radial Artery Patency Study Investigators. A
randomized comparison of radial-artery and saphenous-vein coronary bypass grafts. N Engl J Med.
2004 Nov 25; 351(22):2302-9.
Deb S, Cohen EA, Singh SK, Une D, Laupacis A, Fremes SE; RAPS Investigators. Radial artery andsaphenous vein patency more than 5 years after coronary artery bypass surgery: results from RAPS
(Radial Artery Patency Study). J Am Coll Cardiol. 2012 Jul 3; 60(1):28-35.
Gaudino M, Benedetto U, Fremes S, et al. Association of Radial Artery Graft vs Saphenous Vein Graft
With Long-term Cardiovascular Outcomes Among Patients Undergoing Coronary Artery Bypass
Grafting:
A
SystematicReviewandMeta-analysis.
JAMA.
2020;324(2):179-187.
doi:10.1001/jama.2020.8228
Gaudino M, Alexander JH, Bakaeen FG, Ballman K, Barili F, Calafiore AM, Davierwala P, Goldman S,
Kappetein P, Lorusso R, Mylotte D, Pagano D, Ruel M, Schwann T, Suma H, Taggart DP, Tranbaugh
RF, Fremes S. Randomized comparison of the clinical outcome of single versus multiple arterial grafts:
the ROMA trial-rationale and study protocol. Eur J Cardiothoracic Surg. 2017 Dec 1; 52(6):1031-1040.

1

B.
Positions and Honors
Positions and Employment
2002 - present
Associate Member - Institute Health Policy, Management and Evaluation, Schoolof Graduate Studies, University of Toronto, Toronto Ontario
2001 - present
Professor, Surgery, University of Toronto, Toronto, Ontario
1996 - present
Senior Scientist, Sunnybrook Health Sciences Centre, Toronto, Ontario
1999 - 2013
Head, Cardiovascular Surgery, SHSC, Toronto, Ontario
1999 - 2009
Adjunct Scientist, Cardiovascular Surgery, Institute for Clinical Evaluative Sciences,Toronto, Ontario
1995 - 2002
Research Director, Heart & Circulation Program, SHSC, Toronto, Ontario
1993 - present
Membership, Institute of Medical Science, School of Graduate Studies, University ofToronto, Toronto, Ontario
1989 - present
Staff Surgeon, Cardiovascular Surgery, SHSC, Toronto, Ontario
Other Experience and Professional Membership2022-present
Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology
Focused Update of the Guidelines for the Use of Antiplatelet Therapy
2019-2021
Writing Committee member for Guideline for Coronary Artery Revascularization
ACC/AHA/SCAI
2018-2019
Writing Committee member for Transcatheter Aortic Valve Implantation
Canadian Cardiovascular Society
2016-2017
Writing Committee member for the Management of Heart FailureCanadian Cardiovascular Society
2017 - present
Canadian Cardiovascular Society, Canadian TAVR Guidelines, Canada
2016 – 2020
Canadian Cardiovascular Society, Guidelines Committee, Canada
2016 - present
The Journal of Thoracic and Cardiovascular Surgery, Associate Statistical Editor
2015 - present
LEVO-CTS Steering Committee, Levosimendan in Cardio Thoracic Surgery
2015 - present
The Journal of Thoracic and Cardiovascular Surgery, Associate Statistical Editor
2014 - present
Canadian Journal of Cardiology, Associate Editor
2012 – 2014
Canadian Cardiovascular Society, Canadian CHF Guidelines, Canada
2012 – 2016
Society of Thoracic Surgeons Arterial Conduit Guidelines Committee
2011 - present
National Heart, Lung and Blood Institute Member, ISCHEMIA Surgical Ctte
2009 - present
American College of Chest Physicians, Member, Antithrombotic and Thrombolytic
Therapy: ACCP Clinical Practice Guidelines, 9th Ed2009 - present
Member, CIHR Clinical Investigation D - Peer Review Committee
Honors2010 - 20202015 - 20162005 - 2006
1993 - 1998
1992 - 1993
1988 - 1989
1982 - 1984
C.

Dr. Bernard S. Goldman Chair in Cardiovascular Surgery, Sunnybrook HSC
CentreCharles H. Tator Surgeon-Scientist Mentoring Award, University of Toronto
Lister Prize, University of Toronto
Career Investigator Award, Heart and Stroke Foundation of Canada
George Armstrong Peters Prize, University of Toronto
Heart and Stroke Foundation of Canada - FellowshipHeart and Stroke Foundation of Canada - Fellowship

Contributions to Science

1. Arterial conduits for coronary artery bypass surgery
One of my key scientific contributions has been demonstrating that the radial artery has superior 1-year andlate graft patency compared to the saphenous vein for non-LAD targets, and that radial graft patency isdependent on high grade proximal target vessel stenosis. I was the PI of the CIHR-sponsored multi-centre
longitudinal studies (Radial Artery Patency Study (RAPS), and RAPS-5 Years comparing the angiographic
patency of the radial artery and saphenous vein grafts at 1 year and more than 5 years following surgery. We
also published on the patient and target vessel characteristics associated with 1-year graft patency. The

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important findings were that the severity of target vessel stenosis and peripheral vascular disease wereassociated with radial failure and that female gender and target vessel size with saphenous vein occlusions
graft occlusion. We also showed that the radial artery was effective in diabetic patients. The 1-year
angiographic outcome in diabetic patients was published in Circulation, and the late findings in JTCVS. I
participated in the STS Practice Guidelines of Arterial Conduits which summarized the evidence for the use ofarterial grafts for coronary surgery. Importantly, the radial conduit was considered a Class IIa recommendation,
Level of evidence B. I am currently a member of the AHA/ACC Revascularization Guidelines, for distribution
2021, in which the radial artery received a Class I recommendation, Level of Evidence A.
 Desai ND, Naylor CD, Kiss A, Cohen EA, Feder-Elituv R, Miwa S, Radhakrishnan S, Dubbin J,Schwartz L, Fremes SE, Radial Artery Patency Study Investigators Circulation. 2007 Feb 13;
115(6):684-91. Epub 2007 Feb 5.
 Deb S, Singh SK, Moussa F, Tsubota H, Une D, Kiss A, Tomlinson G, Afshar M, Sless R, Cohen EA,
Radhakrishnan S, Dubbin J, Schwartz L, Fremes SE. Radial Artery Patency Study Investigators. The
long-term impact of diabetes on graft patency after coronary artery bypass grafting surgery: a substudyof the multicenter Radial Artery Patency Study. J Thorac Cardiovasc Surg. 2014 Oct; 148(4):1246-53;
discussion 1253. doi: 10.1016/j.jtcvs.2014.06.057. Epub 2014 Jul 17.
 Aldea GS, Bakaeen FG, Pal J, Fremes S, Head SJ, Sabik J, Rosengart T, Kappetein AP, Thourani VH,Firestone S, Mitchell JD; The Society of Thoracic Surgeons Clinical Practice Guidelines on Arterial
Conduits for Coronary Artery Bypass Grafting.Ann Thorac Surg. 2016 Feb;101(2):801-9. doi:
10.1016/j.athoracsur.2015.09.100. Epub 2015 Dec 8. PMID: 26680310
 Gaudino M, Benedetto U, Fremes S, Biondi-Zoccai G, Sedrakyan A, Puskas JD, Angelini GD, Buxton
B, Frati G, Hare DL, Hayward P, Nasso G, Moat N, Peric M, Yoo KJ, Speziale G, Girardi LN, Taggart
DP; RADIAL Investigators. Radial-Artery or Saphenous-Vein Grafts in Coronary-Artery Bypass Surgery.
N Engl J Med 2018 May 31; 378(22):2069-2077.
 Lawton JS, Tamis-Holland JE, Bangalore S, Bates ER, Beckie TM, Bischoff JM, Bittl JA, Cohen MG,DiMaio JM, Don CW, Fremes SE, Gaudino MF, Goldberger ZD, Grant MC, Jaswal JB, Kurlansky PA,Mehran R, Metkus TS Jr, Nnacheta LC, Rao SV, Sellke FW, Sharma G, Yong CM, Zwischenberger BA.
2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: Executive Summary: A Reportof the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice
Guidelines.Circulation.2022 Jan 18; 45(3): e4-e17.
2. Transcatheter aortic valve replacement (TAVR)
I was the senior author in a systematic review and meta-analysis comparing TAVR and surgical AVR inintermediate risk patients. There was no difference in 30-day and late mortality, while the rate of complicationsdiffered between TAVR and surgical AVR. Cost-effectiveness studies have been completed in intermediaterisk patients comparing balloon expandable TAVR and surgical AVR, and comparing self-expanding TAVR
and surgical AVR. TAVR with balloon expandable devices may be cost-effective for the treatment of severe
aortic stenosis in patients with intermediate surgical risk. More recently, balloon expandable TAVR was foundto be cost effective in low surgical risk patients. A population level study in the province of Ontario, Canadashowed that TAVR v-in-v was a preferred strategy compared to redo surgery for failing bioprostheses in apropensity score matched study. Using discrete event simulation, transcatheter valve durability was found tobe unlikely to affect survival in older low-risk patients, but may affect survival in young patients if durability wassubstantially less than surgical bioprostheses.
 Tam DY, Vo TX, Wijeysundera HC, Ko DT, Rocha RV, Friedrich J, Fremes SE. Transcatheter vssurgical aortic valve replacement for aortic stenosis in low-intermediate risk patients: a meta-analysis.
Can J Cardiol. 2017 Sep; 33(9):1171-1179.
 Tam DY, Azizi PM, Fremes SE, Chikwe J, Gaudino M, Wijeysundera HC. The cost-effectiveness oftranscatheter aortic valve replacement in low surgical risk patients with severe aortic stenosis[published online ahead of print, 2020 Jul 9]. Eur Heart J Qual Care Clin Outcomes. 2020;qcaa058.
doi:10.1093/ehjqcco/qcaa058
 Tam DY, Dharma C, Rocha RV, Ouzounian M, Wijeysundera HC, Austin PC, Chikwe J, Gaudino M,Fremes SE. Transcatheter ViV Versus Redo Surgical AVR for the Management of Failed Biological
Prosthesis: Early and Late Outcomes in a Propensity-Matched Cohort. JACC Cardiovasc Interv.
2020;13(6):765-774. doi:10.1016/j.jcin.2019.10.030

3Tam DY, Wijeysundera HC, Naimark D, Gaudino M, Webb JG, Cohen DJ, Fremes SE. Impact ofTranscatheter Aortic Valve Durability on Life Expectancy in Low-Risk Patients With Severe Aortic
Stenosis. Circulation. 2020;142(4):354-364. doi:10.1161/CIRCULATIONAHA.119.044559

3. Myocardial Protection and Cardiopulmonary bypass Management
I have been a steering committee member and/or Co-Investigator of several large multi-centre RCTs in cardiac
surgery addressing important clinical question over the past 25 years including: CORONARY, SIRS, TRICSIII,LEVO-CTS and SUSTAIN CSX. CORONARY compared on- and off-pump coronary surgery in higher risk
CABG patients (4752 patients) finding that outcomes were similar after on- and off-pump CABG. SIRS
evaluated the role of steroids to reduce mortality in high risk cardiac surgery (7000 patients) and found thathigh dose steroids did not have any beneficial effect on hard clinical outcomes. TRICSIII compared two different
transfusion algorithms (liberal vs. conservative) in high risk cardiac surgery (5243 patients). A restrictive
strategy regarding red-cell transfusion was noninferior to a liberal strategy with respect to the primary
composite outcome, with less blood transfused. LEVO-CTS study evaluated the role of levosimenden inpatients with decreased left ventricular ejection fraction undergoing CABG +/- valve surgery (849 patients).
The 2 co-primary outcomes did not differ between groups although secondary endpoints related to low cardiac
output syndrome did. SUSTAIN CSX which evaluates the role of high dose selenium in high risk cardiac has
completed recruitment.
 Mazer CD, Whitlock RP, Fergusson DA, Hall J, Belley-Cote E, Connolly K, Khanykin B, Gregory AJ, deMédicis É, McGuinness S, Royse A, Carrier FM, Young PJ, Villar JC, Grocott HP, Seeberger MD,Fremes S, Lellouche F, Syed S, Byrne K, Bagshaw SM, Hwang NC, Mehta C, Painter TW, Royse C,Verma S, Hare GMT, Cohen A, Thorpe KE, Jüni P, Shehata N; TRICS Investigators and Perioperative
Anesthesia Clinical Trials Group. Restrictive or Liberal Red-Cell Transfusion for Cardiac Surgery. NEngl J Med. 2017 Nov 30;377(22):2133-2144.
 Mehta RH, Leimberger JD, van Diepen S, Meza J, Wang A, Jankowich R, Harrison RW, Hay D, Fremes
S, Duncan A, Soltesz EG, Luber J, Park S, Argenziano M, Murphy E, Marcel R, Kalavrouziotis D,Nagpal D, Bozinovski J, Toller W, Heringlake M, Goodman SG, Levy JH, Harrington RA, Anstrom KJ,
Alexander JH; LEVO-CTS Investigators. Levosimendan in Patients with Left Ventricular Dysfunction
Undergoing Cardiac Surgery. N Engl J Med. 2017 May 25;376(21):2032-2042.
 Stoppe C, McDonald B, Rex S, Manzanares W, Whitlock R, Fremes S, Fowler R, Lamarche Y,Meybohm P, Haberthür C, Rossaint R, Goetzenich A, Elke G, Day A, Heyland DK. SodiUm SeleniTeAdminstration IN Cardiac Surgery (SUSTAIN CSX-trial): study design of an international multicenter
randomized double-blinded controlled trial of high dose sodium-selenite administration in high-riskcardiac surgical patients. Trials. 2014 Aug 28;15:339.
Complete List of Published Work in My Bibliography:
http://www.ncbi.nlm.nih.gov/pubmed/?term=fremes+s
D. Research Support and/or Scholastic Performance
Canadian Institutes of Health Research (CIHR)
PI: Fremes
04/2022-03/2029
The Canadian CABG or PCI in Patients with Ischemic Cardiomyopathy (STICH 3.0) Trial USD 2,048,291
Role: Principal Investigator
NIH NHLBI
PIs: Gaudino/ M Creber/Swartz
07/2021-06/2026
Randomized Comparison of the Clinical Outcomes of Single versus Multiple Arterial Grafts: Cognition(ROMA:Cog). USD$ 2,498,700
Role: Co-Investigator
09/2021-08/2023
EMHSeed program, University of Toronto
PIs: Jimenez Juan/Craig
A patient-specific experimental and computational platform to identify failure mechanisms of coronary artery
bypass grafts USD 88,221
Role: Collaborator
Boston Scientific Ltd

PI: Sam Radhakrishnan

07/2020-06/2030

4

Accurate IDE Study. USD 352,884
Role: Co-Investigator
NIH NHLBI
PIs: Gaudino/ M Creber
04/2020-03/2025
Randomized Comparison of the Clinical Outcomes of Single versus Multiple Arterial Grafts: Quality of Life(ROMA: QOL). USD$ 4,164,370
Role:Co-Investigator
Canadian Institutes of Health Research (CIHR)
PI: Mazer
10/2020-09/2023
TRICS IV: Transfusion Requirements in Younger Patients Undergoing Cardiac Surgery USD 1,223,784
Role: Co-applicant
Canadian Institutes of Health Research (CIHR)
PI: Andre Lamy
04/2020 – 03/2023
Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery(DEPOSITION Trial). USD 1,165,252
Role: Co-applicant
FED DEV Ontario Grant
PI: Wijeysundera
01/2020-1/2023
REdireCT TAVI Remote Ecg Monitoring to Reduce ComplicaTions following TranscatheterAortic Valve Implantations USD 73,517
Role:Co-Investigator
Canadian Institutes of Health Research (CIHR)
PIs:Whitlock/ Belley-Côté
VISION Cardiac Surgery - ECG Evaluation Sub-Study. USD 393,200
Role: Co-Investigator

04/2020-03/2022

Canadian Institutes of Health Research (CIHR)
PIs: Fremes/Gaudino
04/2019-03/2026
Randomized Comparison of the Clinical Outcome of Single versus Multiple Arterial grafts: the ROMA trial –The Definitive Phase. USD 3,925,495
Role: Principal Investigator
Amgen Inc
PIs: Mazer/Verma
10/2018-03/2023
A randomized trial of evolocumab on saphenous vein graft patency following coronary artery bypass surgery(NEWTON-CABG) USD 403,740
Role: Co-Investigator
Medtronic Inc.
TAVR ‘Low Risk Study’. USD 193,556
Role: Co-Investigator

PI: Sam Radhakrishnan

04/2017-03/2027

Lotte & John Hecht Memorial Foundation.
PI: Darren Keith Heyland
01/2016-08/2020
SodiUm SeleniTe Administration IN Cardiac Surgery (SUSTAIN CSX®-trial). USD 2,193,355
Role: Steering Committee- Co-Investigator- Collaborator
Medtronic Inc. (Physio-Control International Corporation) PIs: Fremes/Radhakrishnan 07/2013-06/2026
Surgical Replacement and Transcatheter Aortic Valve Implantation (SURTAVI). USD 379,904
Role: Co-Principal Investigator5