Remote ischemic preconditioning can extend the tolerance to extended drug-coated balloon inflation time by reducing myocardial damage during percutaneous coronary intervention

https://doi.org/10.1016/j.ijcard.2022.01.049Get rights and content

Highlights

  • This study suggests that short-term preoperative RIPC can increase the DCB inflation tolerance time.

  • The short-term application of RIPC before operation can reduce myocardial injury secondary to PCI.

  • The larger the ischemic area of RIPC, the more significant the improvement of DCB tolerance time.

Abstract

Background

Remote ischemic preconditioning (RIPC) alleviates myocardial ischemia-reperfusion injury (IRI) that occurs during percutaneous coronary intervention (PCI) and increases the myocardial tolerance to ischemia and hypoxia. Prolonged inflation time of drug-coated balloons (DCBs) can improve the treatment effects of PCI and the long-term prognosis of patients. This study investigated whether preoperative RIPC improves the tolerance to extended DCB inflation time.

Methods and results

Overall, 345 patients with coronary artery disease (CAD) were enrolled; 90, 96, 83, and 76 of these were randomized into the upper limb RIPC, lower limb RIPC, upper limb control, and lower limb control groups, respectively. Their baseline data were collected. Data on cardiac markers were analyzed. The DCB inflation time was recorded. The baseline data and cardiac marker levels before operation did not differ between RIPC and control groups. The post-PCI high-sensitivity troponin-T levels were lower in the RIPC groups (35.81 ± 14.02 and 34.65 ± 14.86 pg/mL) than in the control groups (41.63 ± 18.31 and 42.24 ± 14.38 pg/mL) (P = 0.001). The DCB inflation tolerance time was higher in the lower limb RIPC group (120 s [120,120]) than in the upper limb RIPC group (120 s [110,120]), and was the lowest in the upper limb control (100 s [90, 120]) and the lower limb control (100 s [90, 115]) groups (P < 0.001).

Conclusions

RIPC reduces the level of myocardial damage that occurs during PCI and prolongs tolerance to increased DCB inflation time. The larger the ischemic area in RIPC, the better the improvement in the tolerance to extended DCB inflation time.

Introduction

Drug-coated balloons (DCBs) comprise a novel strategy for percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD). They have become one of the leading choices for in-stent restenosis (ISR), and are reportedly superior to drug-eluting stents (DES) in the management of branch-opening lesions and small vessel disease. Their use reduces the changes to the coronary artery anatomy, risk of late postoperative thrombosis, and application time of dual antiplatelet drugs [1], [2]. Studies have shown that DCB has a dose-dependent inhibitory effect on intimal hyperplasia. As the DCB inflation time increases, the concentration of the drug in the coronary artery wall also increases gradually, whereas the incidences of target lesion revascularization (TLR), TLR failure, and target vessel revascularization decrease significantly. Therefore, increasing the inflation time of DCB improves its therapeutic effect, thereby improving the patients' long-term prognoses [3], [4], [5]. However, directly increasing the DCB inflation time may aggravate angina pectoris, decrease the patient's blood pressure, and promote severe reperfusion arrhythmia.

Remote ischemic preconditioning (RIPC) refers to the repeated short-term and noninvasive ischemic preconditioning of remote organs (e.g., the mesentery, kidney, limbs, etc.) to reduce the risk of an ischemia-reperfusion injury (IRI) secondary to acute ischemia of vital organs via the activation of several neural and humoral signal pathways [6], [7]. The evidence on RIPC-led cardioprotection is inconclusive. Some studies have reported an increased infarct size in patients undergoing PCI or receiving a coronary artery bypass graft (CABG) with RIPC [8], [9]; however, most studies have observed that RIPC protects the coronary microcirculation [10] and the myocardium [11] from IRI, thereby reducing the incidence of periprocedural myocardial infarction [12]. We speculate that a preoperative RIPC treatment can prolong the DCB inflation tolerance time by reducing the incidence of IRI, and thus, improve the long-term prognosis of patients with CAD. Therefore, this study aimed to observe whether the use of RIPC before PCI can prolong the tolerance time to DCB inflation.

Section snippets

Patients

This study included 345 patients with CAD who presented to our hospital between January 2018 and January 2020. Overall, 90, 96, 83, and 76 patients were randomized into the upper limb (UL) RIPC, lower limb (LL) RIPC, UL control, and LL control groups, respectively.

The inclusion criteria were as follows: (1) a diagnosis of CAD, (2) age ≤ 80 year; (3) coronary angiography-derived diagnosis of in situ, de novo lesions of a single coronary artery; (4) target vessel diameter ≥ 2.75 mm; (5) target

Baseline data

There were no statistically significant differences among the four groups in terms of the clinical data (Supplementary Table S1), including the sex; age; BMI; history of smoking; history of hypertension, diabetes, and dyslipidemia; drug use; angina pectoris grade (CCS classification) and cardiac function (NYHA classification); LVEF; and peripheral blood myoglobin and high-sensitivity troponin-T levels 2 h before the operation. The features of the coronary lesion and duration of the operation

Discussion

To the best of our knowledge, this is the first study to report an increased tolerance to an extended DCB inflation time following RIPC performed prior to PCI. DESs are widely used in patients with CAD undergoing PCI; however, due to the hollow structure of the stent, anti-proliferative drugs are unevenly distributed in the blood vessel wall. Furthermore, application of excipients inhibits endothelialization at the attachment site of the stent; due to this and long-term exposure, the stent is

Conclusion

This study explored the relationship between RIPC, myocardial injury, and tolerance to extended DCB inflation time during coronary intervention. We found that RIPC extended the tolerance of patients to extended DCB inflation time by alleviating myocardial injury. RIPC has several advantages as a treatment method, including its simplicity, low cost, non-invasiveness, and high safety. It can be smoothly implemented in clinics to improve the treatment effect in patients with CAD and could improve

Funding

This work was supported by the Henan Provincial Health Commission [grant number: LHGJ20190780] and Department of Science and Technology of Henan Province [grant number: 202300410465].

CRediT authorship contribution statement

Zhenzhou Zhao: Methodology, Funding acquisition, Writing – original draft. Qingbo Shi: Investigation, Writing – original draft. Quan Guo: Formal analysis. Liang Peng: Resources. Xuejie Li: Writing – review & editing. Lixin Rao: Writing – review & editing. Muwei Li: Supervision, Funding acquisition.

Declaration of Competing Interest

None.

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    These two authors contributed equally to this work.

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