Daily remote ischaemic conditioning following acute myocardial infarction: a randomised controlled trial

Andrew Peter Vanezis, Jayanth Ranjit Arnold, Glenn Rodrigo, Florence Y Lai, Radek Debiec, Sheraz Nazir, Jamal Nasir Khan, Leong L Ng, Kamal Chitkara, John G Coghlan, Simon Lee Hetherington, Gerry P McCann, Nilesh J Samani, Andrew Peter Vanezis, Jayanth Ranjit Arnold, Glenn Rodrigo, Florence Y Lai, Radek Debiec, Sheraz Nazir, Jamal Nasir Khan, Leong L Ng, Kamal Chitkara, John G Coghlan, Simon Lee Hetherington, Gerry P McCann, Nilesh J Samani

Abstract

Background: Remote ischaemic conditioning (rIC) is a cardioprotective tool which has shown promise in preclinical and clinical trials in the context of acute ischaemia. Repeated rIC post myocardial infarction may provide additional benefits which have not previously been tested clinically.

Methods: The trial assessed the role of daily rIC in enhancing left ventricular ejection fraction (LVEF) recovery in patients with impaired LVEF (<45%) after ST segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (P-PCI). Patients were recruited from four UK hospitals and randomised to receive either 4 weeks of daily rIC or sham conditioning using the autoRIC Device (CellAegis) starting on day 3 post P-PCI. The primary endpoint was the improvement in LVEF over 4 months assessed by cardiac MRI (CMR). Seventy-three patients (38 cases, 35 controls) completed the study.

Results: The treatment and control groups were well matched at baseline including for mean LVEF (42.8% vs 44.3% respectively, p=0.952). There was no difference in the improvement in LVEF over 4 months between the treatment and control groups (4.8%±7.8% vs 4.6%±5.9% respectively, p=0.924). No differences were seen in the secondary outcome measures including changes in infarct size and left ventricular end-diastolic and systolic volumes, major adverse cardiac and cerebral event, mean Kansas City Cardiomyopathy Questionnaire score and change in N-terminal pro-brain natriuretic peptide levels.

Conclusions: Daily rIC starting on day 3 and continued for 4 weeks following successful P-PCI for STEMI did not improve LVEF as assessed by CMR after 4 months when compared with a matched control group.

Trial registration number: NCT0166461.

Trial registration: ClinicalTrials.gov NCT01664611.

Keywords: ST elevation myocardial infarction; heart failure; primary percutaneous coronary intervention; remote ischaemic conditioning; ventricular remodelling.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Participant flow diagram—CONSORT (Consolidated Standards of Reporting Trials) diagram of recruitment to the trial. CMR, cardiac MRI; LVEF, left ventricular ejection fraction.
Figure 2
Figure 2
Cardiac MRI (CMR) assessment of left ventricular ejection fraction (LVEF) at baseline and 4 months—d ifference in LVEF as assessed by CMR from baseline scan to 4-month scan in the control (blue) versus treatment (orange) groups.

References

    1. Heusch G, Bøtker HE, Przyklenk K, et al. . Remote ischemic conditioning. J Am Coll Cardiol 2015;65:177–95. 10.1016/j.jacc.2014.10.031
    1. Kharbanda RK, Mortensen UM, White PA, et al. . Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation In 2002;106:2881–3. 10.1161/01.CIR.0000043806.51912.9B
    1. Kleinbongard P, Skyschally A, Heusch G. Cardioprotection by remote ischemic conditioning and its signal transduction. Pflugers Arch 2017;469:159–81. 10.1007/s00424-016-1922-6
    1. Sloth AD, Schmidt MR, Munk K, et al. . Improved long-term clinical outcomes in patients with ST-elevation myocardial infarction undergoing remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention. Eur Heart J 2014;35:168–75. 10.1093/eurheartj/eht369
    1. Munk K, Andersen NH, Schmidt MR, et al. . Remote Ischemic Conditioning in Patients With Myocardial Infarction Treated With Primary Angioplasty: Impact on Left Ventricular Function Assessed by Comprehensive Echocardiography and Gated Single-Photon Emission CT. Circ Cardiovasc Imaging 2010;3:656–62. 10.1161/CIRCIMAGING.110.957340
    1. Elbadawi A, Ha LD, Abuzaid AS, et al. . Meta-Analysis of Randomized Trials on Remote Ischemic Conditioning During Primary Percutaneous Coronary Intervention in Patients With ST-Segment Elevation Myocardial Infarction. Am J Cardiol 2017;119:832–8. 10.1016/j.amjcard.2016.11.036
    1. Schmidt MR, Rasmussen ME, Bøtker HE. Remote Ischemic Conditioning for Patients With STEMI. J Cardiovasc Pharmacol Ther 2017;22:302–9. 10.1177/1074248417702481
    1. Bøtker HE, Kharbanda R, Schmidt MR, 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. Lancet 2010;375:727–34. 10.1016/S0140-6736(09)62001-8
    1. Verouhis D, Sörensson P, Gourine A, et al. . Effect of remote ischemic conditioning on infarct size in patients with anterior ST-elevation myocardial infarction. Am Heart J 2016;181:66–73. 10.1016/j.ahj.2016.08.004
    1. Wei M, Xin P, Li S, et al. . Repeated remote ischemic postconditioning protects against adverse left ventricular remodeling and improves survival in a rat model of myocardial infarction. Circ Res 2011;108:1220–5. 10.1161/CIRCRESAHA.110.236190
    1. Nazir SA, McCann GP, Greenwood JP, et al. . Strategies to attenuate micro-vascular obstruction during P-PCI: the randomized reperfusion facilitated by local adjunctive therapy in ST-elevation myocardial infarction trial. Eur Heart J 2016;37:1910–9. 10.1093/eurheartj/ehw136
    1. Hudsmith LE, Petersen SE, Tyler DJ, et al. . Determination of cardiac volumes and mass with FLASH and SSFP cine sequences at 1.5 vs. 3 Tesla: a validation study. J Magn Reson Imaging 2006;24:312–8. 10.1002/jmri.20638
    1. Omland T, Persson A, Ng L, et al. . N-terminal pro-B-type natriuretic peptide and long-term mortality in acute coronary syndromes. Circulation 2002;106:2913–8. 10.1161/
    1. Ottervanger JP, van ’t Hof AW, Reiffers S, et al. . Long-term recovery of left ventricular function after primary angioplasty for acute myocardial infarction. Eur Heart J 2001;22:785–90. 10.1053/euhj.2000.2316
    1. Baks T, van Geuns RJ, Biagini E, et al. . Recovery of left ventricular function after primary angioplasty for acute myocardial infarction. Eur Heart J 2005;26:1070–7. 10.1093/eurheartj/ehi131
    1. Solomon SD, Glynn RJ, Greaves S, et al. . Recovery of ventricular function after myocardial infarction in the reperfusion era: the healing and early afterload reducing therapy study. Ann Intern Med 2001;134:451–8. 10.7326/0003-4819-134-6-200103200-00009
    1. Klug G, Metzler B. Assessing myocardial recovery following ST-segment elevation myocardial infarction: short- and long-term perspectives using cardiovascular magnetic resonance. Expert Rev Cardiovasc Ther 2013;11:203–19. 10.1586/erc.12.173
    1. Bell RM, Bøtker HE, Carr RD, et al. . 9th Hatter Biannual Meeting: position document on ischaemia/reperfusion injury, conditioning and the ten commandments of cardioprotection. Basic Res Cardiol 2016;111:41 10.1007/s00395-016-0558-1
    1. Shimizu M, Saxena P, Konstantinov IE, et al. . Remote ischemic preconditioning decreases adhesion and selectively modifies functional responses of human neutrophils. J Surg Res 2010;158:155–61. 10.1016/j.jss.2008.08.010
    1. Yamaguchi T, Izumi Y, Nakamura Y, et al. . Repeated remote ischemic conditioning attenuates left ventricular remodeling via exosome-mediated intercellular communication on chronic heart failure after myocardial infarction. Int J Cardiol 2015;178:239–46. 10.1016/j.ijcard.2014.10.144
    1. Vanezis AP, Edroos SA, Samani NJ, et al. . The inhibitory effect of remote ischaemic conditioning on a cellular model of cardiac hypertrophy. Heart 2012;98(Suppl 5):A4.4–A5. 10.1136/heartjnl-2012-303148a.13
    1. Jones H, Hopkins N, Bailey TG, et al. . Seven-day remote ischemic preconditioning improves local and systemic endothelial function and microcirculation in healthy humans. Am J Hypertens 2014;27:918–25. 10.1093/ajh/hpu004
    1. Hombach V, Grebe O, Merkle N, et al. . Sequelae of acute myocardial infarction regarding cardiac structure and function and their prognostic significance as assessed by magnetic resonance imaging. Eur Heart J 2005;26:549–57. 10.1093/eurheartj/ehi147
    1. Konstam MA, Kramer DG, Patel AR, et al. . Left ventricular remodeling in heart failure: current concepts in clinical significance and assessment. JACC Cardiovasc Imaging 2011;4:98–108. 10.1016/j.jcmg.2010.10.008
    1. Brenner S, Ertl G. Remodelling and adverse remodelling in CAD. Herz 2012;37:590–7. 10.1007/s00059-012-3660-7
    1. Pryds K, Nielsen RR, Jorsal A, et al. . Effect of long-term remote ischemic conditioning in patients with chronic ischemic heart failure. Basic Res Cardiol 2017;112:67 10.1007/s00395-017-0658-6
    1. Pfeffer MA, Lamas GA, Vaughan DE, et al. . Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction. N Engl J Med 1988;319:80–6. 10.1056/NEJM198807143190204
    1. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet 2001;357:1385–90.
    1. Tsutamoto T, Wada A, Maeda K, et al. . Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure. J Am Coll Cardiol 2001;37:1228–33. 10.1016/S0735-1097(01)01116-0
    1. Miki T, Itoh T, Sunaga D, et al. . Effects of diabetes on myocardial infarct size and cardioprotection by preconditioning and postconditioning. Cardiovasc Diabetol 2012;11:67 10.1186/1475-2840-11-67

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner