minimise the damage – pre- and post-conditioning dr derek j hausenloy the hatter cardiovascular...
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Minimise the damage – Pre- and Post-conditioning
Dr Derek J Hausenloy
The Hatter Cardiovascular Institute,
University College London, UK.
Myocardial Recovery Session
ADVANCED CARDIOVASCULAR INTERVENTION 2010
London, Thursday January 28th 2010.
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NO CONFLICT OF INTEREST TO DECLARE
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• Novel treatment strategies are required to reduce myocardial injury and improve clinical outcomes.
• ‘Conditioning’ the heart is an endogenous protective phenomenon.
• Pre- and Post- Conditioning offer novel strategies for minimising the damage.
Background
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What is Pre- and Post- condtioning?
No ‘Conditioning’
Heart Ischaemia Reperfusion‘Conditioned’
Ischaemic Postconditioning
2003
< 1min
Ischaemic Preconditioning
1986, 1993
0 to 3 hrs12-24 hrs
CABG surgeryCardiac Tx
NSTEMI undergoing PCIElective PCI
CABG surgeryCardiac Tx
Cardiac arrestSTEMI
CABG surgerySTEMI
Cardiac TxCardiac arrest
Remote Ischaemic Preconditioning
Remote Ischaemic Perconditioning
Remote Ischaemic Postconditioning
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RIPC in CABG surgeryHausenloy et al Lancet 2007:370;575.
• CK-MB/Trop release during CABG surgery.
• 57 adult CABG patients: RIPC- 3x5 min cuff inflation Control- 30 min deflated cuff
• RIPC reduced myocardial injury by 43%.
• Beneficial in CABG patients receiving cardioplegia alone (Venugopal et al Heart 2009).
• Beneficial in congenital heart disease and AAA surgery (Cheung et al JACC 2006, Ali et al Circ 2007).
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• 200 elective PCI patients:
RIPC- 3x5 min cuff inflation
Control- 30 min deflated cuff
• RIPC reduced median trop I from 0.16 to 0.06 and increased number of trop negative patients from 24 to 42%.
RIPC in elective PCI Hoole et al Circ 2009:92;1821.
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RIPerC in PPCI patients Botker et al Lancet In Press Feb 2010
• 246 STEMI patients randomised in ambulance to RIPC 4x5 min cuff on arm or control.
• DANAMI network• All comers.
- Myocardial salvage index improved at 30 days (0.56 to 0.76).
- Reduced myocardial infarct size at 30 days (SPECT P=0.05)
- No effect on Troponin-T, TIMI flow, LVEF, MACE at 30 days.
- All coronary territories, TIMI 2-3 flow and collaterals included.
-LAD infarcts greater reduction in infarct size.
- Future studies should focus on specific patients.
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• 30 STEMI pts:
Control- Normal PPCI
IPost- 4x1 min inflations/deflations
• IPost reduced myocardial injury by 36%.
Ischaemic Postconditioning in PPCIStaat et al Circ 2005:112;2143.
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1. Improved myocardial perfusion and ST resolution 1,2
2. Reduced myocardial infarct size: 40% less CK-MB, 47% less trop I 4. 31% to 23% at 1 week (SPECT) 3. 20% to 12% at 6 mths (SPECT) 4.
63% to 51% (IS/AAR) at 3 months (N=86) 5.
3. Preserved LV ejection function by 7% (echo) at 1 year 4.
1. Staat et al Circ 2005
2. Ma et al J Interven Cardiol 2006
3. Yang et al J Interven Cardiol 2007
4. Thibault et al Circ 2008
5. Lonborg et al Circ Card Int 2010
Ischaemic Postconditioning in PPCI
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Ischemic Postconditioning in SurgeryLuo et al J Thorac Cardiovasc Surg 2007:133;1373.
• 24 children TOF surgery:
Control- Normal surgery
IPost- 2x30 sec aortic re-clamping.
• Reduced trop-I by 50% and CK-MB by 34%.
• Invasive treatment protocol.
• Other studies reporting benefit in adult valve surgery.
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Pharm Postconditioning using CsA Piot et al NEJM 2008;359:473.
• 58 STEMI patients (TIMI 0): Saline placebo or
IV CsA 2.5 mg/kg prior to PPCI (<10min).
• Reduced Trop-I by 26% (P=NS) CK by 36%, and CMR 20% (27 patients).
• Most benefit for larger infarcts (>40% AAR).
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Pharm Postconditioning using EPO Ludman et al Unpublished 2010.
• 51 STEMI patients (TIMI 0): Saline placebo or
IV EPO 50,000 IU prior to PPCI and 24 hr later.
• Trend to increased IS.
• Doubling of MVO, acute LV dilatation and increased myocardial mass.
Acute EndpointsEndpoint Placebo EPO P value
AUC Trop-T (µg/l) 102 ± 68 115 ± 78 NS
Infarct (% of LV) 16 ± 9 19 ± 9 NS
LGE/AAR (%) 61 ± 23 66 ± 20 NS
Myocardial salvage index 0.41 ± 0.24 0.36 ± 0.20 NS
MVO (% incidence) 42 82 0.02*
LVEF (%) 53 ± 10 51 ± 7 NS
LVEDVi (ml/m2) 73 ± 13 84 ± 10 0.003*
LVESVi (ml/m2) 34 ± 11 41 ± 9 0.036*
LVMi (g/m2) 79 ± 11 89 ± 16 0.031*
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Conclusions
• Endogenous ‘conditioning’ strategies can be applied prior to or during ischaemia or at the onset of reperfusion.
• RIPC beneficial in cardiac surgery, AAA surgery, elective PCI, PPCI.
• Ischaemic and pharmacological postconditioning beneficial in PPCI patients.
• Large multi-centre clinical studies required to determine the effect on clinical outcomes.
• Potential benefit in cardiac arrest, cardiac transplantation, stroke and other surgical settings.
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Professor Derek Yellon
Dr Peter Mwamure
Dr Vinod Venugopal
Staff and patients at the Heart Hospital and Royal Free Hospital
British Heart Foundation
Acknowledgements