Principal Investigator: Associate Professor Theodoros Kofidis

MD, PD(Ger), FAHA, FAMS

Senior Consultant Department of Cardiac, Thoracic & Vascular Surgery, NUHCS
Head Division of Adult Cardiac Surgery, Dept of CTVS
Director Robotic Cardiac Surgery Program
Chairman Initiative for Research and Innovation of Surgery (IRIS)
Associate Professor Department of Surgery, Yong Loo Lin School of Medicine, NUS

Research Lab Profile:

Myocardial Restoration

Minimally Invasive Cardiac Surgery and Devices

 

Research Theme:

Heart Surgery Research / Less Invasive and Restorative Technologies 

  

GROUP MEMBERS

  • Rufaihah Binte Abdul Jalil
  • Pal Nagesh Shripad
  • Vu Duc Thang
  • Do Thi Di Thien
  • Ocampo Marquez Ervin
  • Min Zin Oo
  • Cheyyatraivendran Arularasu Suganya
  • Wang Jing
  • Oh Hyun Rim
  • Ong Chin Siang
  • Luo Haidong

COLLABORATORS

  • Lee Chuen Neng, NUS
  • Philip Keith Moore, NUS
  • Ti Lian Kah, NUHS
  • Chen Lujie, SUTD
  • Dror Seliktar, Technion Institute, Israel
  • Marcelle Machluf, Technion Institute, Israel
  • Ong Lay Choo, NYP, Singapore
  • Neo Poh Hock, NYP, Singapore
  • Ulrich Schraudolph, XentiQ Pte Ltd

PUBLICATIONS

No. of papers published : 109

Intl. Review/Submitted/in press: 12

H-Index = 26

Citation index: 3156

 

Selected Publications

1.  Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium.

     Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC.

Nature. 2004 Apr 8; 428(6983):668-73. (Impact Factor 38.597)

 

2.  Novel Injectable bioartificial tissue facilitates targeted, less invasive, large-scale tissue restoration on the beating heart after myocardial injury.

Kofidis T, Lebl DR, Martinez EC, Hoyt G, Tanaka M, Robbins RC.

Circulation 2005 Aug 30; 112(9 Suppl):I173-7. (Impact Factor 15.202)

 

3. Stimulation of paracrine pathways with growth factors enhances embryonic stem cell engraftment and host-specific differentiation in the heart after ischemic myocardial injury.

     Kofidis T, de Bruin JL, Yamane T, Tanaka M, Lebl DR, Swijnenburg RJ, Weissman IL, Robbins RC. Circulation. 2005 May 17; 111(19):2486-93. (Impact Factor 15.202)

 

4.  Novel, sutureless mitral valve implantation method involving a bayonet insertion and release mechanism: a proof-of-concept study in pigs.

Vu DT, Ti LK, Ong LC, Neo PH, Lee CN, Kofidis T.

Journal of Thoracic and Cardiovascular Surgery. 2012 Apr;143(4):985-988(Impact Factor 3.526).

 

5.   A novel and simple atrial retractor.

Kofidis T and Lee CN.

Annals of Thoracic Surgery, vol. 91, pp. 1634-5, May 2011. (Impact Factor 3.454).

 

6.    Off-pump coronary bypass surgery is safe in patients with a low ejection fraction (< or =25%).

      Emmert MY, Emmert LS, Martinez EC, Lee CN, Kofidis T.

Journal of Thoracic and Cardiovascular Surgery. 2010 Jun; 13(3):E136-42. (Impact Factor 0.458)

 

7.    Off-pump coronary bypass grafting is safe and efficient in patients with left main disease and higher EuroScore.

Thomas GN, Martinez EC, Woitek F, Emmert MY, Sakaguchi H, Muecke S, Lee CN, Kofidis T. European Journal of Cardio-thoracic Surgery. 2009 Oct; 36(4):616-620. (Impact Factor 2.674)

 

8.  Adenoviral human BCL-2 transgene expression attenuates early donor cell death after cardiomyoblast transplantation into ischemic rat hearts.

Kutschka I, Kofidis T, Chen IY, von Degenfeld G, Zwierzchoniewska M, Hoyt G, Arai T, Lebl DR, Hendry SL, Sheikh AY, Cooke DT, Connolly A, Blau HM, Gambhir SS, Robbins RC.

Circulation. 2006 Jul 4; 114(1 Suppl):I174-80. (Impact Factor 15.202)

 

9.  Collagen matrices enhance survival of transplanted cardiomyoblasts and contribute to functional improvement of ischemic rat hearts.

Kutschka I, Chen IY, Kofidis T, Arai T, von Degenfeld G, Sheikh AY, Hendry SL, Pearl J, Hoyt G, Sista R, Yang PC, Blau HM, Gambhir SS, Robbins RC.

Circulation. 2006 Jul 4; 114 (1 Suppl):I167-73. (Impact Factor 15.202)


10. Overexpression of human copper/zinc superoxide dismutase (SOD1) suppresses ischemia-reperfusion injury and subsequent development of graft coronary artery disease in murine cardiac grafts.

Tanaka M, Mokhtari GK, Terry RD, Balsam LB, Lee KH, Kofidis T, Tsao PS, Robbins RC.

Circulation 2004 Sep 14; 110 (11 Suppl 1):II200-6. (Impact Factor 15.202)

 

11. Suppression of graft coronary artery disease by a brief treatment with a selective epsilonPKC activator and a deltaPKC inhibitor in murine cardiac allografts.

Tanaka M, Terry RD, Mokhtari GK, Inagaki K, Koyanagi T, Kofidis T, Mochly-Rosen D, Robbins RC. Circulation 2004 Sep 14;110(11 Suppl 1):II194-9. (Impact Factor 15.202)

 

12. Cardiomyocyte-specific Bcl-2 overexpression attenuates ischemia-reperfusion injury, immune response during acute rejection, and graft coronary artery disease.

Tanaka M, Nakae S, Terry RD, Mokhtari GK, Gunawan F, Balsam LB, Kaneda H, Kofidis T, Tsao PS, Robbins RC

Blood. 2004 Dec 1;104(12):3789-96. (Impact Factor 9.060)

 

Book Chapters

  1. Boehler A, Kofidis T, et al. Thorakale Organtransplantation – Eine Standortbestimmung. SteinkopffPubl. Darmstadt, Germany, 2002.
  2. Kofidis T, Klima U  et al. Gene Theraoy in Biotechnology. Wissenschafltiche Verlagsgesellschaft mbH Stuttgart; ISBN: 3-8407-1917-1. Kapitelbeitrag: “Gentherapie in der Chirurgie“, Seite 358.W. Harringer,
  3. Kofidis T: Tacrolimus in der Herz- und Lungentransplantation. Pabst Science Publishers. 2002. Lengerich, Germany.
  4. Kofidis T, Robbins RC. Nanobiology and Nanotechnology in Cardiology and Cardiac Surgery, CRC Press, Fl,USA.
  5. Kofidis T, Haverich A. In vivo generation of bioartificial tissues and organs. in press; Humana Press. NJ, USA. 
  6. Kofidis T et al. (ch. 11) in “Lagerungstechniken im Operationsbereich. Springer, Heidelberg 2005.

FUNDING SUPPORT

  • Centre Grant Devices and Less Invasive Surgery for Heart Failure. Co PI, SGD1,000,000
  • NMRC IRG 10May71 Promoting Effective Lymphatic Drainage of the Arteries as a New Therapeutic Intervention for Atherosclerosis. Co-I, $932,205, Jan 2011 – Dec 2013
  • SUTD-MIT Internation Design Centre (IDC) Research Grant. Infrared 3-Dimensional Imaging for Cardiac Procedures. PI, $712,000, Jul 2012 – Jun 2015,
  • NRF-Technion Singapore Project (Thrust 2 - Cell Therapy Using Injectable, Resorbable, Biocompatible Materials) Regenerative Medicine Initiative in Cardiac Restoration Therapy. PI, S$3.7M, 5 years (Oct 2009 –Sep 2014
  • Effect of sodium hydrosulfide (NaHS) in ischemia-reperfusion injury in the rat cardiopulmonary bypass (CPB) model. Co-I, $8000
  • NMRC CIRG. Transatrial, Catheter-based Valve Implantation on the Beating Heart. PI, 950,000. Aug 2013- Jul 2015

 

BRIEF

At NUHS, the department of CTVS has become a hub of minimally invasive procedures. We have extensive experience in minimally invasive, aortic, mitral, tricuspid valve operations. We have recently started our-catheter based valve program. In the past few years we have placed great focus on research, winning grants & awards, while our interest progressively shifted towards medical devices and minimally invasive procedure.

Associate-Prof Kofidis has pioneered the minimally invasive heart surgery and robotic program at our department. The team has received HDMP-funded subspecialty training in Europe & the US. He & his team have a long track record in animal research with prominent international presence. He has started the CTVS laboratory at NUHS and introduced minimally invasive operations in rats and pigs using minimally invasive tools.

Furthermore, the team has carried out large animal experiments, ranging from low risk-high risk procedures. Many of them involved cardiopulmonary bypass to develop a novel, sutureless mitral valve prosthesis (published in Journal of Thoracic and Cardiovascular Surgery). In addition, we are manufacturing minimally invasive instruments, such as left atrial retractor, which significantly reduce trauma and cost for the patient undergoing mitral valve surgery.

In our recently concluded NMRC project,we targeted the injured heart muscle, not only by repopulating it with cells but also geometrically restoring it. This approach was undertaken in an acute stage of myocardial infarctions, remodeling and ensuing heart failure in a large animal model.

Overall, the findings from this study suggest a role for a novel restorative compound in improving LV functions and limiting remodeling in an acute myocardial infarction model. These results lays a platform for randomized clinical trails in patients incurring significant acute myocardial loss despite current best-practice management of acute myocardial infarction and who are at clear risk of major adverse ventricular remodeling in the short to intermediate term post- infarction

One of our two new NMRC funded projects include developing a minimally invasive, single incision trans-atrial, cather-based heart valve implantation that would be safe, easy, fast and efficient in a clinical environment. The success of the study would address a vast number of patients’ degenerative mitral regurgitation, mitral stenosis and degenerative bioprosthesis disease.  We expect this approach to become for application for emerging technologies, such as novel, expandable heart valves, surgical aspects and imaging tools. The strength of this proposal lies in the immediate translational potential. Because of its minimal invasiveness, more high risk patients can be cured by catheter-based valves. Tricuspid and mitral valve diseases can be addressed in the same session this simple and more direct approach. 

Our second project would focus on developing the concept of Cardioscopic Surgery that will permit access to multiple pathologies at the same time (aortic, mitral, tricuspid, vascular, arrhythmias) in a large animal model. This project involving transapical cardioscopic surgery is proposed to treat multiple pathologies in a single intervention, in a minimally invasive way, avoiding sternotomy, which is very critical in heart failure patients. Our preliminary data showed that this novel surgical approach is feasible. With further refinement and instrumental development, we will be able to exploit the full potential of this approach. We expect to see this procedure less invasive, in terms of trauma to the body and the heart that would help the heart to recover faster and experience less dysfunction postoperatively. At the same time the modality of large animal cardiopulmonary bypass, with various types of open heart surgery, will be a strong addition to the core capacities of the CVRI at NUHCS, and establish a invaluable platform for heart and circulation related studies in the future with immense clinical significance.