Chronic Remote Ischemic Conditioning Treatment in Patients with Chronic Stable Angina (EARLY-MYO-CSA): a Randomized, Controlled Proof-of-concept Trial

Overview

Journal BMC Med

Publisher Biomed Central

Specialty General Medicine

Date 2023 Aug 25

PMID 37626410

Authors

Quan Guo

Zhenzhou Zhao

Fan Yang

Zhiwen Zhang

Xiaoyu Rao

Jing Cui

Qingbo Shi

Kaiyuan Liu

Kang Zhao

Haiyu Tang

Liang Peng

Cao Ma

Jun Pu

Muwei Li

Affiliations

Soon will be listed here.

Abstract

Background: Chronic remote ischemic conditioning (CRIC) has been shown to improve myocardial ischemia in experimental animal studies; however, its effectiveness in patients with chronic stable angina (CSA) has not been investigated. We conducted a proof-of-concept study to investigate the efficacy and safety of a six-month CRIC treatment in patients with CSA.

Methods: The EARLY-MYO-CSA trial was a prospective, randomized, controlled trial evaluating the CRIC treatment in patients with CSA with persistent angina pectoris despite receiving ≥ 3-month guideline-recommended optimal medical therapy. The CRIC and control groups received CRIC (at 200 mmHg) or sham CRIC (at 60 mmHg) intervention for 6 months, respectively. The primary endpoint was the 6-month change of myocardial flow reserve (MFR) on single-photon emission computed tomography. The secondary endpoints were changes in rest and stress myocardial blood flow (MBF), angina severity according to the Canadian Cardiovascular Society (CCS) classification, the Seattle Angina Questionnaire (SAQ), and a 6-min walk test (6-MWT).

Results: Among 220 randomized CSA patients, 208 (105 in the CRIC group, and 103 in the control group) completed the treatment and endpoint assessments. The mean change in MFR was significantly greater in the CRIC group than in the control group (0.27 ± 0.38 vs. - 0.04 ± 0.25; P < 0.001). MFR increased from 1.33 ± 0.48 at baseline to 1.61 ± 0.53 (P < 0.001) in the CRIC group; however, a similar increase was not seen in the control group (1.35 ± 0.45 at baseline and 1.31 ± 0.44 at follow-up, P = 0.757). CRIC treatment, when compared with controls, demonstrated improvements in angina symptoms assessed by CCS classification (60.0% vs. 14.6%, P < 0.001), all SAQ dimensions scores (P < 0.001), and 6-MWT distances (440 [400-523] vs. 420 [330-475] m, P = 0.016). The incidence of major adverse cardiovascular events was similar between the groups.

Conclusions: CSA patients benefit from 6-month CRIC treatment with improvements in MFR, angina symptoms, and exercise performance. This treatment is well-tolerated and can be recommended for symptom relief in this clinical population.

Trial Registration: [chictr.org.cn], identifier [ChiCTR2000038649].

References

Sousa-Uva M, Neumann F, Ahlsson A, Alfonso F, Banning A, Benedetto U . 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur J Cardiothorac Surg. 2018; 55(1):4-90. DOI: 10.1093/ejcts/ezy289. View

Davies A, Fox K, Galassi A, Banai S, Yla-Herttuala S, Luscher T . Management of refractory angina: an update. Eur Heart J. 2020; 42(3):269-283. DOI: 10.1093/eurheartj/ehaa820. View

Zhao Z, Shi Q, Guo Q, Peng L, Li X, Rao L . Remote ischemic preconditioning can extend the tolerance to extended drug-coated balloon inflation time by reducing myocardial damage during percutaneous coronary intervention. Int J Cardiol. 2022; 353:3-8. DOI: 10.1016/j.ijcard.2022.01.049. View

Heusch G, Gersh B . The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge. Eur Heart J. 2016; 38(11):774-784. DOI: 10.1093/eurheartj/ehw224. View

Lau J, Roy P, Javadzadegan A, Moshfegh A, Fearon W, Ng M . Remote Ischemic Preconditioning Acutely Improves Coronary Microcirculatory Function. J Am Heart Assoc. 2018; 7(19):e009058. PMC: 6404904. DOI: 10.1161/JAHA.118.009058. View

Heusch G . Myocardial ischaemia-reperfusion injury and cardioprotection in perspective. Nat Rev Cardiol. 2020; 17(12):773-789. DOI: 10.1038/s41569-020-0403-y. View

Hausenloy D, Botker H, Engstrom T, Erlinge D, Heusch G, Ibanez B . Targeting reperfusion injury in patients with ST-segment elevation myocardial infarction: trials and tribulations. Eur Heart J. 2016; 38(13):935-941. PMC: 5381598. DOI: 10.1093/eurheartj/ehw145. View

Xu Y, Yu Q, Yang J, Yuan F, Zhong Y, Zhou Z . Acute Hemodynamic Effects of Remote Ischemic Preconditioning on Coronary Perfusion Pressure and Coronary Collateral Blood Flow in Coronary Heart Disease. Acta Cardiol Sin. 2018; 34(4):299-306. PMC: 6066945. DOI: 10.6515/ACS.201807_34(4).20180317A. View

McLeod S, Iansavichene A, Cheskes S . Remote Ischemic Perconditioning to Reduce Reperfusion Injury During Acute ST-Segment-Elevation Myocardial Infarction: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2017; 6(5). PMC: 5524098. DOI: 10.1161/JAHA.117.005522. View

10.

Pryds K, Nielsen R, Hoff C, Tolbod L, Bouchelouche K, Li J . Effect of remote ischemic conditioning on myocardial perfusion in patients with suspected ischemic coronary artery disease. J Nucl Cardiol. 2016; 25(3):887-896. DOI: 10.1007/s12350-016-0709-7. View

11.

Chong J, Bulluck H, Ho A, Boisvert W, Hausenloy D . Chronic remote ischemic conditioning for cardiovascular protection. Cond Med. 2020; 2(4):164-169. PMC: 7169952. View

12.

Hausenloy D, Ng C, Chong J . Repeated Remote Ischemic Conditioning Protects Against Doxorubicin Cardiotoxicity: Never Too Much of a Good Thing. JACC CardioOncol. 2021; 2(1):53-55. PMC: 8352202. DOI: 10.1016/j.jaccao.2020.02.001. View

13.

Pryds K, Nielsen R, Jorsal A, Hansen M, Ringgaard S, Refsgaard J . Effect of long-term remote ischemic conditioning in patients with chronic ischemic heart failure. Basic Res Cardiol. 2017; 112(6):67. DOI: 10.1007/s00395-017-0658-6. View

14.

Badruzzaman Khan M, Hafez S, Hoda M, Baban B, Wagner J, Awad M . Chronic Remote Ischemic Conditioning Is Cerebroprotective and Induces Vascular Remodeling in a VCID Model. Transl Stroke Res. 2017; 9(1):51-63. PMC: 5750336. DOI: 10.1007/s12975-017-0555-1. View

15.

Ding J, Shang S, Sun Z, Asmaro K, Li W, Yang Q . Remote ischemic conditioning for the treatment of ischemic moyamoya disease. CNS Neurosci Ther. 2019; 26(5):549-557. PMC: 7163773. DOI: 10.1111/cns.13279. View

16.

Chen Q, Huang M, Wu J, Jiang Q, Zheng X . Exosomes isolated from the plasma of remote ischemic conditioning rats improved cardiac function and angiogenesis after myocardial infarction through targeting Hsp70. Aging (Albany NY). 2020; 12(4):3682-3693. PMC: 7066898. DOI: 10.18632/aging.102837. View

17.

Kono Y, Fukuda S, Hanatani A, Nakanishi K, Otsuka K, Taguchi H . Remote ischemic conditioning improves coronary microcirculation in healthy subjects and patients with heart failure. Drug Des Devel Ther. 2014; 8:1175-81. PMC: 4154883. DOI: 10.2147/DDDT.S68715. View

18.

Kottenberg E, Thielmann M, Kleinbongard P, Frey U, Heine T, Jakob H . Myocardial protection by remote ischaemic pre-conditioning is abolished in sulphonylurea-treated diabetics undergoing coronary revascularisation. Acta Anaesthesiol Scand. 2014; 58(4):453-62. DOI: 10.1111/aas.12278. View

19.

Chan H, Chang C, Hu C, Wang W, Peng N, Tyan Y . The Evaluation of Left Ventricle Ischemic Extent in Patients with Significantly Suspicious Cardiovascular Disease by Tc-Sestamibi Dynamic SPECT/CT and Myocardial Perfusion Imaging: A Head-to-Head Comparison. Diagnostics (Basel). 2021; 11(6). PMC: 8234843. DOI: 10.3390/diagnostics11061101. View

20.

Johnson N, Gould K . Integrating noninvasive absolute flow, coronary flow reserve, and ischemic thresholds into a comprehensive map of physiological severity. JACC Cardiovasc Imaging. 2012; 5(4):430-40. DOI: 10.1016/j.jcmg.2011.12.014. View