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Advances in Surgical Therapies for Heart Failure: Innovative Approaches and Techniques

This presentation by Magdi Yacoub highlights the latest developments in surgical therapies for heart failure (HF). Key topics include revascularization, mechanical lesion correction, surgical remodeling, transplantation, and the use of left ventricular assist devices (LVAD). The discussion also addresses challenges such as donor shortages and immune tolerance in transplantation. Furthermore, it emphasizes the importance of combination therapies and the molecular and cellular mechanisms involved in heart failure. Continued innovation in these areas is critical for improving patient outcomes.

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Advances in Surgical Therapies for Heart Failure: Innovative Approaches and Techniques

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  1. Surgical therapies in HF, New Developments Magdi Yacoub FRS . Madrid May 6. 2010

  2. Surgical therapies in HF, New Developments Procedures • Revascularization • Correcting Mechanical Lesions • Surgical Remodeling • Transplantation • LVAD • Combinations

  3. Surgical therapies in HF, New Developments Correcting Mechanical Lesions • Rupture of IV Septum • MR result depend on pathophysiology • LV aneurysmectomy • DOR (Stitch trial) • ACCORN (prevent dilatation)

  4. Surgical therapies in HF, New Developments Transplantation • Dealing with donor shortage • Legislation • Ex vivo perfusion (transmedics) • Inducing specific immune tolerance • Several trial in Renal and liver TX

  5. Surgical therapies in HF, New Developments LVAD • Bridge to transplantation • Destination therapy • Bridge to recovery • Platfom for other form of therapy

  6. Surgical therapies in HF, New Developments Systems: RAS Organ: Changes in ventricular shape; laplace vs starling Multicellular: Connexins, Matrix abnormalities Cellular: CICR; Metabolic dysfunction; Cell loss etc Molecular: Ion Channel abnormalities…

  7. Surgical therapies in HF, New Developments LVAD -Bridge to Transplantation Reduced late Survival after bridge to transplantaion Shuhiber, BMj 2010 Left ventricular assist devices.  From an imaginative leap to clinical decision making M Yacoub, Nature reviews April 2010

  8. Surgical therapies in HF, New Developments LVAD - Bridge to Recovery • Defining mechanism of revascular remodeling • Benifetial and harmful effect of unloading

  9. The t-tubule system

  10. A site of concentration of ion channels Gu et al FASEBJ

  11. * Z Orientation 100 K X (TEM-Padmini)

  12. Calcium-induced calcium release (Cesare Terracciano)

  13. Techniques: patch clamping APs (current-clamp) A pulse of current triggers the AP and the voltage trace is recorded L-type current (voltage-clamp) -- 40mV to + 40mV +/- Cd

  14. F/Fo 10 µm 50 ms Techniques: Confocal

  15. FS

  16. CICR after prolonged overload Gomez et al 1997 Science Song et al 2006PNAS Lyon et al 2009 PNAS

  17. T-tubule disruption in HF

  18. T-tubules are critical for synchronous calcium release Human Atrial Cell few Rat Ventricle abundant HF Lost/disordered

  19. Conclusions • Continued development in many aspect of Heart Failure • Emphasis on combination therapies

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