A 2 part presentation. Part 1 reviews a paper on the long-term clinical outcomes of STEMI patients undergoing remote ischaemic perconditioning prior to primary percutaneous coronary intervention. The 2nd part looks at how this technique can be used in Paramedic practice.

2.  Describe the procedure of Remote Ischaemic
Conditioning
 Review the paper
 Discuss how this could relate to future
paramedic practice
 Answer any questions

3. Brief overview & procedure

4. What is Remote
Ischaemic
Conditioning?
 Remote ischemic conditioning (RIC) is a therapeutic strategy for protecting organs or
tissue against the detrimental effects of acute ischemia-reperfusion injury (IRI). (Lim
and Hausenloy, 2012)
 It was first discovered by Murry et al. in 1986 who described a phenomenon in which
the application of one or more brief cycles of non-lethal ischemia and reperfusion to an
organ or tissue protects a remote organ or tissue from a sustained episode of lethal
ischaemia-reperfusion injury. (Lim and Hausenloy, 2012)
So, in simpler terms…
‘It is a method of protecting organs or tissues from damage and
reperfusion complications occurring after blood flow and
oxygenation is restored to the area. It also increases recovery of
damaged tissue and thus reduces long-term health complications.’
Overview

5. What is Remote
Ischaemic
Conditioning?
 Nobody really knows yet.
 The precise mechanism is still unclear
(Le Page and Prunier, 2015)
 It is believed that the cells exposed to
the small periods of ischaemia either
produce a protective substance which
enters the circulatory system, or the
ischaemic cells open nervous
pathways to the brain, which in turn
relays nervous impulses to the other
areas of ischaemia and causes them
to release a chemical.
How does it work?
Sivaraman et al. 2015

6. What is Remote
Ischaemic
Conditioning?
In the majority of
studies utilising
remote ischaemic
per-conditioning
this method is the
procedure used.
Procedure
Place cuff on
patients arm
Inflate to
200mmHg
Leave
inflated for 5
minutes
Deflate cuff
and allow
reperfusion of
arm for 5
minutes
Repeat
process 3
more times

7. What is Remote
Ischaemic
Conditioning?
Uses
PRE-ISCHAEMIC CONDITIONING
Used prior to an ischaemic event, such as cardiac surgery.
PER-ISCHAEMIC CONDITIONING
Used during an ischaemic event, such as on a STEMI patient prior to pPCI.
POST-ISCHAEMIC CONDITIONING
Following an ischaemic event for a period of time, most commonly used after pPCI.
Remote Ischaemic Conditioning can be sub-divided into 3 different methods, each can be used
in different situations:

8. Aims, Methodology, Results, Conclusion, Limitations, Related Studies

9. The Article
The Authors and History
Published in the European
Heart Journal in 2014.
AUTHORS
• Led by Astrid Sloth – a research fellow at Aarhus University Hospital,
Denmark
• The authors have amassed a total of 426+ publications between
them all (www.pubfacts.net), on many subjects ranging from RIC to
neonatal pig resuscitation.
FUNDING
• The research was funded by the Danish Council for Strategic
Research and Foundation Leducq.
• The design, conduction, analysis, interpretation and reporting of the
trial was independent of both funding sources.
DECLARATION OF INTERESTS
• 4 of the authors are shareholders in ‘CellAegis’ – a company that
makes an automatic RIC machine.
• No other conflicts of interest were reported.

10. • The aims of this trial were based on a follow up from the results of a parent trial by
Botker et al. which was published in The Lancet in 2010:
‘Remote Ischaemic Conditioning Before Hospital Admission, As A ComplimentTo
Angioplasty, And Effect On Myocardial Salvage In Patients With Acute Myocardial
Infarction: A RandomisedTrial’
• This trial concluded patients who had remote ischaemic conditioning performed
prior to primary percutaneous coronary intervention had an increase in myocardial
salvage post procedure compared to those that did not.
This secondary trial was designed to investigate the long-
term clinical outcome of patients receiving remote ischaemic
conditioning as an adjunct to primary percutaneous coronary
intervention.

11. SYSTEMATIC
REVIEW & META
ANALYSIS
RANDOMISED
CONTROLLEDTRIALS
COHORT STUDIES
CASE-CONTROL STUDIES
CASE SERIES / CASE REPORTS
EDITORIALS / EXPERT OPINION

12. • >18 years
AGE
• <12h prior to admission
SYMPTOM DURATION
• >0.1mV in two or more contiguous ECG leads
ST-SEGMENT ELEVATION

13. • Not confirmed on arrival at hospital
DIAGNOSIS
• History of previous Myocardial Infarction
• History of previous Coronary Artery Bypass Graft (CABG)
HISTORY
• Chest pain onset >12h prior to admission
SYMPTOM ONSET

14. Methodology
TRIAL PERIOD:
February 2007 – November 2008
TOTAL PATIENTS ENROLLED:
333
RIC+pPCI (intervention group):
166
(40 did not meet trial criteria)
Final amount: 126
pPCI ONLY (control group):
167
(42 did not meet trial criteria)
Final amount: 125
OUTCOMES MEASURED
DAY 1-30
Salvage Index / LV function
YEAR 5
MACCE (majoradverse cardiac or cerebral event)
Trial Flowchart

15. • Patients meeting the inclusion criteria received
Remote Ischaemic Conditioning initiated in the
ambulance during transport to pPCI.
• 82 patients were excluded from the trial on arrival at
hospital as they did not meet the described trial
criteria.

16. Methodology
This study used 4
cycles of
inflation/deflation
with both periods
lasting 5 minutes.
Technique Used
INFLATE 5 MINS
DEFLATE 5 MINS
INFLATE 5 MINS
DEFLATE 5 MINS
INFLATE 5 MINS
DEFLATE 5 MINS
INFLATE 5 MINS
Place cuff on
patients arm
Inflate to
200mmHg
Leave
inflated for 5
minutes
Deflate cuff
and allow
reperfusion
of arm for 5
minutes
Repeat
process 3
more times

17. PRIMARY ENDPOINTS SECONDARY ENDPOINTS
MACCE
‘MAJOR ADVERSE CARDIAC
AND CEREBROVASCULAR
EVENTS’
Defined as a composite of:
• All-cause mortality*
• Myocardial infarction
• Readmission for heart failure
• Ischaemic stroke/TIA
Comprised of the individual components of
the primary endpoint.
• All-cause mortality*
• Myocardial infarction
• Readmission for heart failure
• Ischaemic stroke/TIA
* ‘ALL-CAUSE MORTALITY’ WAS DEFINED AS ANY DEATH OCCURING WITHIN THE FOLLOW-UP PERIOD, THIS WAS SUB-DIVIDED INTO ‘CARDIAC’ AND
‘NON-CARDIAC DEATHS’. CARDIAC DEATHS WERE DEFINED AS DEATHS WITH AN EVIDENT CARDIAC CAUSE OR DEATH FROM AN UNKNOWN CAUSE.

19. pPCI WITH RIC
(126 PATIENTS)
13.5%
(n17)
pPCI WITHOUT RIC
(126 PATIENTS)
25.6%
(n32)
PRIMARY ENDPOINT
(MACCE OCURRING IN THE 3 YEAR FOLLOW UP PERIOD)

21. SECONDARY ENDPOINTS
ALL CAUSE
MORTALITY
pPCI WITH RIC
pPCI
WITHOUT RIC
CARDIAC
MORTALITY
pPCI WITH RIC
pPCI
WITHOUT RIC
NON-CARDIAC
MORTALITY
pPCI WITH RIC
pPCI
WITHOUT RIC
n5(4.9%) vs n15(12.0%) n2(1.6%) vs n5(4.0%) n3(2.4%) vs n10(8.0%)
ALL CAUSE MORTALITY reduced in patients who had RIC prior to pPCI
• Reduced CARDIAC MORTALITY (2 vs 5)
• Reduced NON-CARDIAC MORTALITY (3 vs 10)

22. SECONDARY ENDPOINTS
MYOCARDIAL
INFARCTION
pPCI WITH RIC
pPCI
WITHOUT RIC
N-STEMI
pPCI WITH RIC
pPCI
WITHOUT RIC
STEMI
pPCI WITH RIC
pPCI
WITHOUT RIC
n8(6.4%) vs n11(8.8%) n2(1.6%) vs n4(3.2%) n6(4.8%) vs n7(5.6%)
• 8 patients had a second Myocardial Infarction within the 3 year follow up period if they
had RIC prior to pPCI, compared to 11 that did not have RIC.
• The incidence of STEMI was higher in the non-RIC group however there was no
significant difference in N-STEMI between both groups.

23. SECONDARY ENDPOINTS
READMISSION FOR
HEART FAILURE
pPCI WITH RIC
pPCI
WITHOUT RIC
DECOMPENSATED
CHRONIC/ACUTE
HEART FAILURE
pPCI WITH RIC
pPCI
WITHOUT RIC
DEVICE
IMPLANTATION
(ICD/BIV-…
pPCI WITH RIC
pPCI
WITHOUT RIC
n4(3.2%) vs n7(5.6%) n3(2.4%) vs n3(2.4%) n1(0.8%) vs n4(3.2%)
• 7 patients who did not receive RIC were readmitted to hospital due to heart failure,
compared to 4 who were.
• There was no difference in the incidence of Acute Heart Failure in both groups of
patients.
• Only 1 patient who received RIC required pacemaker/internal defibrillator implantation,
whereas 4 who did not receive RIC did.

24. SECONDARY ENDPOINTS
ISCHAEMIC
STROKE/TIA
pPCI WITH RIC
pPCI
WITHOUT RIC
STROKE
pPCI WITH RIC
pPCI
WITHOUT RIC
TIA
pPCI WITH RIC
pPCI
WITHOUT RIC
n3(2.4%) vs n4(3.2%) n2(1.6%) vs n4(3.2%) n1(0.8%) vs n0(0.0%)
• 3 patients had an ischaemic stroke orTIA in the ‘received RIC’ group, compared to 4
patients who did not have RIC.
• All 4 of these patients had a stroke.
• 1 patient from the ‘received RIC’ group had aTIA, with none from the without RIC group
having aTIA.

25. • A P-value of <0.05 was considered statistically significant
in this study.
• The primary endpoints investigated met this (P-value
0.018), however only the ‘All-Cause Mortality’ secondary
endpoint was classed as being statistically significant.

26. ‘Remote ischaemic conditioning
before primary percutaneous
coronary intervention seemed to
improve long-term clinical
outcomes in patients with ST-
elevation myocardial infarction.’

27. ‘However, our results need to be
confirmed in a larger multicentre
trial before remote ischaemic
conditioning can be implemented
in guidelines as an adjunct to
primary percutaneous coronary
intervention.’

28. The number of patients involved is small
• This meant a number of secondary endpoints were not
classed as statistically significant
Exclusion Criteria
• Almost 25% of the patients from the original trial were
excluded from the results due to not meeting criteria
The process is open to bias
• Paramedics performing RIC would of known they were
doing the procedure, it could not be blinded.

29. STUDY AUTHORS OUTCOME
Cardioprotective Role Of Remote
Ischemic Periconditioning In
Primary Percutaneous Coronary
Intervention: Enhancement By
Opioid Action.
Rentoukas et al.
Reduced Troponin levels in STEMI patients
treated with RIC & Morphine compared to
control group.
Remote Ischemic Post-
conditioning OfThe Lower Limb
During Primary Percutaneous
Coronary Intervention Safely
Reduces Enzymatic Infarct Size In
Anterior Myocardial Infarction: A
Randomized ControlledTrial.
Crimi et al.
Reduced myocardial oedema and increased
ST segment resolution in the group of
patients who received RIC.
Remote Ischaemic Conditioning
Reduces Myocardial Infarct Size
And Myocardial Oedema In
Patients With ST-segment
Elevation Myocardial Infarction
White et al.
Reduced infarct size, myocardial oedema and
Troponin levels.
Increased myocardial salvage.

30. Does it have a place and what are its uses?

31. • Cardiovascular disease is the leading cause of death in the UK, in 2013-2014 a total of 80,724
patients were admitted to hospital suffering from a Myocardial Infarction (Myocardial
Ischaemia National Audit Project [MINAP], 2014).
• The development and implementation of novel adjuvant strategies to attenuate myocardial
ischaemia-reperfusion injury and reduce infarct size remains a major, unmet clinical need.
(Przyklenk, 2015)
• For patients with ischaemic heart disease, remote ischaemic conditioning may offer an
innovative, non-invasive and virtually cost-free therapy for protecting the myocardium
against the detrimental effects of acute ischaemia-reperfusion injury, preserving cardiac
function and improving clinical outcomes. (Sivaraman, Pickard and Hausenloy, 2015)
• ‘Ischaemic conditioning’ has the therapeutic potential to protect the heart against acute
ischaemia/reperfusion injury (IRI) and improve clinical outcomes in patients with ischaemic
heart disease, the leading cause of death and disability worldwide. (Bulluck and Hausenloy,
2015)

32. STEMI
• Reduced mortality
• Improved long-term
health outcomes
• Can be used alongside
current practice
ISCHAEMIC
STROKE
• Increased tissue
survival (Hougaard et
al. 2013)
POST
ROSC
• Reduced markers of
cell damage when
applied immediately
after ROSC (Albrecht
et al. 2015)

33. NON INVASIVE, EFFECTIVE AND SAFE
Remote Ischaemic Conditioning is non-invasive, effective, and free of both cost and side-effects. (Vercueil, 2015)
NOT AFFECTED BY PHARMACOLOGY
RIC as an adjunct to pPCI seems to improve the Myocardial Salvage Index of patients with STEMI regardless of medications. (Sloth et al, 2015)
ENHANCED WHEN USED WITH MORPHINE
The cardioprotective effect of RIC is enhanced with Morphine use and reduced reperfusion injury in patients undergoing pPCI. (Rentoukas et al. 2010)
CHEAP
For patients with ischaemic heart disease, remote ischaemic conditioning may offer an innovative, non-invasive and virtually cost-free therapy for protecting the myocardium against
the detrimental effects of acute ischaemia-reperfusion injury, preserving cardiac function and improving clinical outcomes. (Sivaraman, Pickard and Hausenloy, 2015)
USES EQUIPMENT ALREADY AVAILABLE ON AMBULANCES
NEEDS LITTLE TRAINING
CAN BE USED ALONGSIDE CURRENT TREATMENT AND PATHWAYS
FOR

34. AGAINST
• Causes some discomfort

35. 80,724
20,311
14,908
• Patients suffering
Myocardial Infarction in
2013-2014 (MINAP,
2014)
• Admitted via
Ambulance directly or
via transfer with STEMI
for pPCI (MINAP, 2014)
• 26.6% removed due to
not meeting criteria
THEORETICALLY IFTHE RESULTS OFTHIS STUDYWERE APPLIEDTO 2013-2014…
BY APPLYINGTHE 13.5& vs 25.6% 5YEAR SURVIVAL RATES…

36. 1,803 EXTRA PATIENTS
SURVIVINGTO 5YEARS
IT COULD RESULT IN…

37. OTHER
APPLICATIONS
OF ISCHAEMIC
CONDITIONING
CARDIAC
STROKE
TRAUMA
RENAL
CARDIAC
ARREST

38. • In ischaemic stroke patients tissue survival analysis suggests that prehospital RIC may have immediate
neuroprotective effects. (Hougaard et al, 2013)
ISCHAEMIC STROKES
• In patients with ST-elevation myocardial infarction, RIC before percutaneous coronary intervention reduced
the incidence of contrast inducedAcute Kidney Injury. (Yamanaka et al, 2015)
POST pPCI KIDNEY INJURY PREVENTION
• RIC provided perioperative myocardial protection and improved the prognosis of patients undergoingCABG
surgery. (Thielmann et al, 2013)
POST CARDIAC SURGERY
• SAH represents a clinical condition suitable for a proof-of-concept trial for the application of preconditioning
(Koch & Gonzalez, 2013)
SUBARACHNOID HAEMORRHAGE
• RIC applied immediately after ROSC reduces serum concentrations of markers for cell damage and improves
end-systolic pressure volume relationship 4 h after ROSC. (Albrecht et al, 2015)
POST ROSC
• RIC significantly decreased the standard biomarkers of acute brain injury in patients with severeTBI. (Joseph
et al, 2015)
TRAUMATIC BRAIN INJURY
• The beneficial effects of RIC in organ protection during the Shock/Resuscitation phase of care suggest a role
for the application of RIC in the early post-trauma period. (Leung et al, 2015)
SHOCK

39. STUDY DETAILS
Effect of RIC on Clinical Outcomes in
STEMI Patients Undergoing pPCI
(CONDI2)
The aim of the study is to investigate whether RIC can
improve clinical outcomes (cardiovascular death and
heart failure) at one year in patients presenting with
ST-elevation Myocardial Infarction and undergoing
pPCI.
Effect Of Remote Ischaemic
PreconditioningOn Clinical Outcomes
In Patients Undergoing Coronary
Artery Bypass Graft Surgery (ERICCA)
To determine the effect of RIC on Major Adverse
Cardiac and Cerebral Events (MACCE) 12 months after
cardiac surgery. MACCE include cardiovascular (CV)
death, myocardial infarction, revascularisation, and
stroke.

40. The increasing insight into the mechanisms behind the cardioprotective effects of RIC has
uncovered several targets for pharmacological intervention that potentially may partly
reproduce the effects of mechanical conditioning. (Schmidt, Redington and Botker, 2014)

41. • The results of this study and others are encouraging - they have been shown to improve the
outcomes of patients and the procedure is adaptable to many different situations.
• An increasing number of treatments and pathways are being made available to pre-
hospital clinicians treating these patients, this is something that can be used in
combination with these and is not affected by them.
• It is a very low risk non-invasive procedure.
• In times of money and resource limitations this does not require any additional investment
or equipment and very little training.

42. THANK YOU FOR
LISTENING
ANY QUESTIONS?

43. Bøtker, H., Kharbanda, R., Schmidt, M., Bøttcher, M., Kaltoft, A., Terkelsen, C., Munk, K., Andersen, N., Hansen, T., Trautner, S., Lassen, J., Christiansen, E., Krusell, L., Kristensen, S., Thuesen, L., Nielsen, S., Rehling, M., Sørensen, H., Redington, A.,Nielsen, T. (2010). Remote Ischaemic
Conditioning Before Hospital Admission, As A Complement To Angioplasty, And Effect On Myocardial Salvage In Patients With Acute Myocardial Infarction: A Randomised Trial. The Lancet, 375(9716), pp.727-734 [Online] Available at: http://www.ncbi.nlm.nih.gov/pubmed/20189026
(Accessed 18 June 2015)
Bulluck, H., Hausenloy, D. (2015). Ischaemic Conditioning: Are We There Yet? Heart, 101(13), pp.1067-1077 [Online] Available at: http://www.ncbi.nlm.nih.gov/pubmed/25887783 (Accessed 5 June 2015)
Crimi, G., Pica, S., Raineri, C., Bramucci, E., De Ferrari, G., Klersy, C., Ferlini, M., Marinoni, B., Repetto, A., Romeo, M., Rosti, V., Massa, M., Raisaro, A., Leonardi, S., Rubartelli, P., Oltrona Visconti, L., Ferrario, M. (2013). Remote Ischemic Post-conditioning Of The Lower Limb During
Primary Percutaneous Coronary Intervention Safely Reduces Enzymatic Infarct Size In Anterior Myocardial Infarction. JACC: Cardiovascular Interventions, 6(10), pp.1055-1063 [Online] Available at: http://www.ncbi.nlm.nih.gov/pubmed/24156966 (Accessed 5 June 2015)
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