Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 30  |  Issue : 4  |  Page : 1162-1167

Different methods of remote ischemic preconditioning and its effect on outcome of elective percutaneous coronary intervention


1 Cardiology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Cardiology Department, National Heart Institute, Egypt

Date of Submission23-Aug-2015
Date of Acceptance08-Nov-2015
Date of Web Publication04-Apr-2018

Correspondence Address:
Mohamed R Mahmoud
14 El Wehda El Arabya St., Elharam, Giza
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_348_15

Rights and Permissions
  Abstract 


Objective
The purpose of this study was to assess and compare different methods of remote ischemic preconditioning (RIPC) to reduce cardiac myonecrosis as measured by evaluating cardiac troponin I (cTnI) after elective percutaneous coronary intervention (PCI) and to reduce major adverse cardiac event rate at 6 months of follow-up.
Background
RIPC is a way to reduce cardiac myonecrosis.
Patients and methods
This study was conducted on 120 symptomatic patients with coronary heart disease who were scheduled for elective PCI. Patients were randomized into three groups: group A included 40 patients who underwent RIPC immediately before PCI through the upper arm; group B included 40 patients who underwent RIPC immediately before PCI through the upper thigh; and group C (the control group) included 40 patients with no RIPC.
Results
Results of the current study showed that ST-segment deviation during intervention was statistically significantly lower (P < 0.05) in the leg and arm groups versus the control group. Results of the current study showed that rise in cTnI was statistically significantly lower (P < 0.05) in the leg and arm groups versus the control group. However, no significant difference was found between the arm and leg groups as regards rise in cTnI. There was no significant difference between groups as regards the incidence of major adverse cardiac event at 6 months.
Conclusion
RIPC is a simple, cheap, well-tolerated procedure that has a significant effect on the reduction in postprocedural elevations of cTnI. RIPC increases the tolerance of the myocardium to ischemia, reduces ischemic chest discomfort during coronary balloon occlusion, reduces ST-segment deviation during intervention, reduces the rise in cTnI release after elective PCI, and appears to reduce subsequent cardiovascular events. RIPC using the upper thigh or upper arm has same protective effects on the myocardium.

Keywords: cardiac troponin I, elective percutaneous coronary intervention, remote ischemic preconditioning


How to cite this article:
Reda AA, Ragy HI, Salem AG, Mahmoud MR. Different methods of remote ischemic preconditioning and its effect on outcome of elective percutaneous coronary intervention. Menoufia Med J 2017;30:1162-7

How to cite this URL:
Reda AA, Ragy HI, Salem AG, Mahmoud MR. Different methods of remote ischemic preconditioning and its effect on outcome of elective percutaneous coronary intervention. Menoufia Med J [serial online] 2017 [cited 2020 Jun 6];30:1162-7. Available from: http://www.mmj.eg.net/text.asp?2017/30/4/1162/229218




  Introduction Top


Decreasing the incidence of morbidity and mortality from coronary artery disease (CAD) will necessitate the early diagnosis and early detection of risk factors for the prevention of CAD and provide optimal care[1]. Elective percutaneous coronary intervention (PCI) is associated with troponin release in approximately one-third of cases[2]. Troponin release is a sensitive and specific marker of myocyte necrosis and infarction resulting from a form of ischemia/reperfusion injury, downstream embolization of atheromatous material, and coronary side-branch occlusion[3].

A number of studies have demonstrated that procedure-related troponin release is associated with subsequent cardiovascular events[4]. Inducing brief nonlethal episodes of ischemia and reperfusion to the heart either before, during, or even after an episode of sustained lethal myocardial ischemia has the capacity to dramatically reduce myocardial injury, a phenomenon termed ischemic preconditioning (IPC), preconditioning, or postconditioning, respectively[5].

Transient sublethal episodes of ischemia before a prolonged ischemia/reperfusion injury, known as IPC, have been shown to reduce the extent of myocardial infarction (MI)[6]. This protection not only acts locally but also can protect distant tissues, a phenomenon known as remote ischemic preconditioning (RIPC), and limits MI size in animal models[7]. RIPC, induced by repeated brief periods of limb ischemia before index ischemia, reduces myocardial injury in patients exposed to predictable ischemia [8–10].

Since the description of IPC as the most powerful intrinsic modality against ischemia–reperfusion injury[6], methods are being developed for optimum clinical use[11]. Pharmacological preconditioning has not gained much clinical ground and ischemia–reperfusion cycles have been used during cardiac surgery[12].

Although IPC has also been applied during angioplasty (regional vessel preconditioning) to reduce inflammation[13] and enzyme leakage[14], concerns about proximal vessel damage and embolization have been raised[15]. More recently, the novel way of applying preconditioning through remote organ (e.g., limb) ischemia–reperfusion cycles has been described[16].


  Patients and Methods Top


This prospective study included 120 symptomatic patients with coronary heart disease who were scheduled for elective PCI. The patients were randomized to three groups: group A included 40 patients who underwent RIPC immediately before PCI through the upper arm; group B included 40 patients who underwent RIPC immediately before PCI through the upper thigh; and group C (the control group) included 40 patients who did not undergo RIPC. This study was conducted on patients fulfilling the following criteria.

Inclusion criteria

Symptomatic patients with CAD who were referred for elective PCI and were 18 years of age or older were included.

Exclusion criteria

Patients were excluded from the study if one or more of the following conditions exist: emergency PCI, elevation of cardiac troponin I (cTnI) before PCI taken at the preadmission clinic, women of child-bearing age, nicorandil or glibenclamide use (preconditioning-mimetic medication and preconditioning-blocking medication, respectively), severe comorbidity or estimated life expectancy less than 6 months, left ventricular ejection fraction less than 40%, left main stem stenosis requiring coronary bypass surgery, systemic hypotension (systolic <90 mmHg), or cardiogenic shock.

All patients included in the study were subjected to the following: complete history taking including (age, sex, special habits of medical importance, presence of hypertension, diabetes mellitus, dyslipidemia, medication prescribed, and family history of ischemic heart disease), general and local examination, kidney function tests, 12-lead surface ECG, and cardiac enzyme measurements. Venous blood samples were collected serially before and 16 h after PCI. cTnI levels were measured.

PCI with the following interventional data was recorded: number of vessels affected, lesion in each vessel (site and type), procedural details in each vessel (balloon dilatation and stenting), special medical treatment, outcome (whether or not successful), and complication of intervention, including major arrhythmias, bleeding, side branch compromise or occlusions, arterial dissection, thrombus formation, abrupt vessel closure, and slow/no-reflow.

Chest pain severity and ECG ST-segment deviation during PCI were observed and recorded whenever it is possible.

Follow-up after 6 months: for major adverse cardiac event (MACE) rate in the form of clinic visit.

Statistical analysis

Data were analyzed using IBM SPSS statistics version 22 (IBM Corp., Armonk, New York, USA) and MedCalc version 13 (MedCalc Software Bvba; Oostende, Belgium). The D'Agostino–Pearson test was used to examine the normality of numerical data distribution. Numerical variables were presented as mean (SD), if normally distributed, or as median (interquartile range), if skewed. Categorical variables were presented as ratio or as number (%).

Comparison of normally distributed numerical data was made using one-way analysis of variance. The Student–Newman–Keuls test was used for multiple post-hoc pairwise comparisons whenever the analysis of variance test revealed a statistically significant difference among the groups. Skewed data were compared using the Kruskal–Wallis test with the application of the Conover test for multiple post-hoc pairwise comparisons whenever the Kruskal–Wallis test revealed a statistically significant difference among the groups. Categorical data were compared using the Pearson c2-test or Fisher's exact test when appropriate. Ordinal data were compared using the c2-test for trend.

A two-sided P value less than 0.05 was considered statistically significant.


  Results Top


This study was conducted on 120 symptomatic patients with coronary heart disease who were scheduled for elective PCI. Patients were randomized to three groups: group A included 40 patients who underwent RIPC immediately before PCI through the upper arm; group B included 40 patients who underwent RIPC immediately before PCI through the upper thigh; and group C (the control group) included 40 patients who did not undergo RIPC.

Results of the current study showed that there was no significant difference between the three groups as regards their age, sex, and risk factors (diabetes, hypertension, smoking, dyslipidemia, and family history of ischemic heart disease) [Table 1].
Table 1: Patients′ characteristics in the three study groups

Click here to view


There was no significant difference between the three study groups as regards coronary angiographic findings [Table 2].
Table 2: Relevant coronary angiographic findings in the three study groups

Click here to view


There was no significant difference between the three study groups as regards details of the PCI procedure except for ST-segment deviation during intervention, which was statistically significantly lower (P< 0.05) in the leg and arm groups versus the control group [Table 3].
Table 3: Details of the percutaneous coronary intervention procedure in the three study groups

Click here to view


There was no significant difference between the three study groups as regards results of laboratory workup, including serum creatinine level and troponin level, before intervention [Table 4].
Table 4: Results of laboratory workup in the three study groups

Click here to view


There was no significant difference between the three study groups as regards results of troponin level after intervention; however, rise in troponin after intervention was statistically significantly lower (P< 0.05) in the leg and arm groups versus the control group, explaining low take off as regards cTnI related to preconditioning protocol; no significant difference was found between the arm and leg groups as regards rise in cTnI [Table 5] and [Figure 1],[Figure 2],[Figure 3],[Figure 4].
Table 5: Troponin level after intervention in the three study groups

Click here to view
Figure 1: Comparison between groups as regards baseline characteristics and risk factors.

Click here to view
Figure 2: Troponin level before intervention.

Click here to view
Figure 3: Troponin level after intervention.

Click here to view
Figure 4: Rise in troponin level after intervention.

Click here to view



  Discussion Top


In the present study, we assessed the ability of RIPC to attenuate cardiac myonecrosis after elective PCI and to reduce MACE rate at 6 months of follow-up.

Participants who received RIPC had significantly less ischemic ECG changes during stent implantation: the control group, 19 (47.5%); the arm group, six (15%); and the leg group, four (10%) (P = 0.002). This result represents the decrease in cardiac myonecrosis in patients who received RIPC. This is consistent with the findings of Heusch et al.[17], who reported that the participants receiving RIPC had significantly less ischemic ECG changes during stent implantation [ECG ST deviation >1 mm in the RIPC group in 37 (36%) patients vs. 55 (56%) patients in the control group (P = 0.005)].

We found that there was no statistically significant difference between the three groups as regards the troponin level after intervention: the control group, 0.03 (0.03–0.08) ng/ml; the arm group, 0.03 (0.02–0.05) ng/ml; and the leg group, 0.03 (0.03–0.05) ng/ml (P = 0.053). However, on comparison of the rising level of troponin from baseline level before and after intervention there was a statistically significant difference between the three groups: the control group, 0.03 (0.02–0.08) ng/ml; the arm group, 0.02 (0.01–0.04) ng/ml; and the leg group 0.02 (0.01–0.03) ng/ml (P = 0.003).

These results indicate that RIPC, administered by means of transient upper and lower limb ischemia, attenuates PCI-related troponin release in patients undergoing elective PCI and appeared to increase the tolerance of the myocardium to ischemia. This is consistent with the findings of Heusch et al.[17], who reported that RIPC applied 1 h before PCI attenuated procedure-related cTnI release, increased the number of patients who had no detectable cTnI release at 24 h, and appeared to increase the tolerance of the myocardium to ischemia.

Hoole et al.[18] evaluated whether RIPC reduces the frequency of myonecrosis and inflammatory response to PCI as measured using cardiac biomarkers [creatine kinase (CK), CK-MB, and cTnI] and inflammatory marker C-reactive protein, respectively.

The mean postprocedural cTnT level was significantly lower in the RIPC group (0.020 vs. 0.047 ng/ml in the control group) (P = 0.047)[18]. Moreover, the number of patients who developed postprocedural MI was much lower in the RIPC group (6 vs. 12 patients in the control group)[18].

In addition, Rashed et al.[19] demonstrated that RIPC before hospital admission in acute myocardial infraction patients increases myocardial salvage, measured using myocardial perfusion imaging as the proportion of the area at risk salvaged by treatment at 30 days.

Another recent study by Hans et al.[20] demonstrated a significant cardioprotective effect of RIPC and morphine during primary PCI for the prevention of reperfusion injury measured as more patients achieved full ST-segment resolution and less peak troponin I levels.

Despite the fact that our study excluded AMI patients, it shares with the above-mentioned trials the proof of cardioprotection achieved with RIPC in the setting of PCI regardless of whether it is elective or primary PCI.

In contrast, they observed that RIPC exacerbated both CK-MB and cTnI release after PCI and enhanced the inflammatory response in the absence of statin therapy in low-risk patients undergoing single-vessel elective PCI (CK-MB in RIPC was 1.33 vs. 3.57 ng/ml in controls, P < 0.01; cTnI, 0.255 vs. 0.804 ng/ml, P < 0.05, respectively at 24 h)[21] Moreover, there were five versus zero (RIPC vs. control) patients who reached cTnI level more than 1 ng/ml at 24 h[21].

The reason for this discrepancy is not clear, but may be attributed to the use of bilateral arm ischemia as the RIPC stimulus together with the small number of patients (41 patients). Moreover, the patients with multivessel disease, venous graft disease, or small-vessel disease were excluded[22].

In the current study, after 6 months of follow-up for MACE rate, there were eight (20%) participants in the control group who presented with unstable angina, four (10%) in the arm group who presented with unstable angina, and five (12.5%) patients in the leg group – four with unstable angina and one with heart failure. In those patients who received RIPC before elective PCI, the MACE rate at 6 months was lower compared with the control group. This is consistent with the findings of Hoole et al.[17], who reported that on follow-up at 6 months after PCI, there were 17 (7.1%) adverse events; among those patients who received RIPC before elective PCI, the MACE rate at 6 months was lower (four acute coronary syndrome vs. 13 events in the control group: 11 acute coronary syndromes, one acute left ventricular failure, and one death) (P = 0.018).

Finally, this study demonstrates that RIPC has therapeutic benefit to reduce ischemic chest discomfort and subsequent MI after elective PCI. We are in need for applying a RIPC before elective PCI. The observed cardioprotection appears to confer sustained benefit, and a larger study to assess the ability of RIPC to reduce MACE after PCI should be undertaken. The use of RIPC to protect the heart from ischemia associated with a therapeutic procedure is clearly attractive, particularly for elective intervention, and this would be an interesting area of further research.

Limitations and recommendations of the study

The cTnI concentration was measured in a single blood sample obtained 16 h after PCI rather than defining the cTnI release profile every 4–6 h. The resultant value may not be the maximum plasma concentration, although it is generally accepted that the maximum concentration occurs between 12 and 24 h after myocyte necrosis. There was only intermediate follow-up (6 months), but long-term follow-up was not carried out in this study to show the impact of our practice on the outcome on long-term basis.

Postprocedural cTnI elevation must be sought in all patients, even in those with no visible angiographic complications. Further investigations and larger randomized trials should be conducted to further evaluate the cardioprotective role of RIPC and to investigate its underlying mechanisms. A larger study should be undertaken to assess the ability of RIPC to reduce MACE following PCI. Large-scale trials are needed with respect to other aspects of RIPC, including, for example, the influence of concomitant pharmacotherapy and comorbid disease (e.g., diabetes mellitus, hyperlipidemia, prior MI, and advanced age).


  Conclusion Top


RIPC is a simple, cheap, well-tolerated procedure that has a significant effect on the reduction of postprocedural elevations of cTnI.

A significant percentage of patients develop post-PCI elevation of cardiac markers without an identifiable angiographic adverse event supporting the theory of distal microembolization as a cause of myonecrosis.

RIPC increases the tolerance of the myocardium to ischemia, reduces ischemic chest discomfort during coronary balloon occlusion, reduces ST-segment deviation during intervention, reduces the rise of cTnI release after elective PCI and appears to reduce subsequent cardiovascular events.

The observed cardioprotection appears to confer sustained benefit, and a larger study to assess the ability of RIPC to reduce MACE after PCI should be undertaken.

RIPC using the upper thigh has protective effects on the myocardium as the same as RIPC using the upper arm.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Reda AA, Abdelazez WF, Yaseen RI, Elsawaf MM. Risk factor profile and in-hospital complications in patients admitted with acute coronary syndrome in Menoufia Governorate. Menoufia Medical J 2014;27:342.  Back to cited text no. 1
    
2.
Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, et al. Heart disease and stroke statistics 2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2007; 115:e69–171.  Back to cited text no. 2
    
3.
Porto I, Blackman DJ, Nicolson D, Niccoli G, Kahn FZ, Ormerod O, et al. What is the incidence of myocardial necrosis in elective patients discharged on the same day following percutaneous coronary intervention?. Heart 2004; 90:1489–1490.  Back to cited text no. 3
    
4.
Porto I, Blackman DJ, Nicolson D, Niccoli G, Kahn FZ, Ormerod O, et al. Release kinetics of serum cardiac troponin I in ischemic myocardial injury. Clin Biochem 1996; 29:587–594.  Back to cited text no. 4
    
5.
Nageh T, Sherwood RA, Harris BM, Thomas MR. Prognostic role of cardiac troponin I after percutaneous coronary intervention in stable coronary disease. Heart 2005; 91:1181–1185.  Back to cited text no. 5
    
6.
Hausenloy DJ, Yellon DM. Preconditioning and postconditioning: underlying mechanisms and clinical application. Atherosclerosis 2009; 204:334–341.  Back to cited text no. 6
    
7.
Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986; 74:1124.  Back to cited text no. 7
    
8.
Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P. Ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation 1993; 87:893–899.  Back to cited text no. 8
    
9.
Kharbanda RK, Mortensen UM, White PA, Kristiansen SB, Schmidt MR, Hoschtitzky JA, et al. Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation 2002; 106:2881–2883.  Back to cited text no. 9
    
10.
Cheung MM, Kharbanda RK, Konstantinov IE, Shimizu M, Frndova H, Li J, et al. Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans. J Am Coll Cardiol 2006; 47:2277–2282.  Back to cited text no. 10
    
11.
Hausenloy DJ, Yellon DM. Preconditioning and postconditioning: united at reperfusion. Pharmacol Ther 2007; 116:173–191.  Back to cited text no. 11
    
12.
Bolli R, Becker L, Gross G, Mentzer R, Balshaw D, Lathrop DA. Myocardial protection at a crossroads: the need for translation into clinical therapy. Circ Res 2004; 95:125–134.  Back to cited text no. 12
    
13.
Pasupathy S, Homer-Vanniasinkam S. Surgical implications of ischemic preconditioning. Arch Surg 2005; 140:405–409. Discussion 410.  Back to cited text no. 13
    
14.
Lee TM, Lin MS, Tsai CH, Chang NC. Effect of ischemic preconditioning on regional release of inflammation markers. Clin Sci 2005; 109:267–269.  Back to cited text no. 14
    
15.
Laskey WK. Beneficial impact of preconditioning during PTCA on creatine kinase release. Circulation 2002; 99:2085–2089.  Back to cited text no. 15
    
16.
Sutsch G, Kiowski W, Bossard A, Luscher TF, Maier W, Vogt P, et al. Use of an emboli containment and retrieval system during percutaneous coronary angioplasty in native coronary arteries. Schweiz Med Wochenschr 2000; 130:1135–1145.  Back to cited text no. 16
    
17.
Heusch G, Schulz R. Remote preconditioning. J Mol Cell Cardiol 2002; 34:1279–1281.  Back to cited text no. 17
    
18.
Hoole SP, Heck PM, Sharples L, Khan SN, Duehmke R, Densem CG, et al. Cardiac remote ischemic preconditioning in coronary stenting (CRISP stent) study. Circulation 2009; 119:820–827.  Back to cited text no. 18
    
19.
Rashed A, Abdeldayem MK, Farag N, Raymond R, Elnaggar W, Sabet S, et al. Effect of remote ischemic preconditioning on outcome of elective percutaneous coronary intervention. J Am Coll Cardiol 2011; 57:E1094.  Back to cited text no. 19
    
20.
Bøtker HE, Kharbanda R, Schmidt MR, Bøttcher M, Kaltoft AK, Terkelsen CJ, et al. 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 2010;375:727-34.  Back to cited text no. 20
    
21.
Rentoukas I, Giannopoulos G, Kaoukis A, Kossyvakis C, Raisakis K, Driva M, et al. Cardioprotective role of remote ischemic periconditioning in primary percutaneous coronary intervention: enhancement by opioid action. JACC: Cardiovascular Interventions 2010; 3:49–55.  Back to cited text no. 21
    
22.
Iliodromitis EK, Kyrzopoulos S, Paraskevaidis IA, Kolocassides KG, Adamopoulos S, Karavolias G, et al. Increased C reactive protein and cardiac enzyme levels after coronary stent implantation. Is there protection by remote ischaemic preconditioning? Heart 2006; 92:1821–1826.  Back to cited text no. 22
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Patients and Methods
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed785    
    Printed11    
    Emailed0    
    PDF Downloaded66    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]