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. 2023 Mar 21;5(3):332-342.
doi: 10.1016/j.jaccao.2022.11.020. eCollection 2023 Jun.

Remote Ischemic Conditioning in Pediatric Cancer Patients Receiving Anthracycline Chemotherapy: A Sham-Controlled Single-Blind Randomized Trial

Yiu-Fai Cheung  1   2 , Vivian Wing-Yi Li  1 , Edwina Kam-Fung So  1 , Frankie Wai-Tsoi Cheng  2 , Jeffery Ping-Wa Yau  2 , Sau-Ying Chiu  2 , Wilfred Hing-Sang Wong  1 , Daniel Ka-Leung Cheuk  2
Affiliations

Remote Ischemic Conditioning in Pediatric Cancer Patients Receiving Anthracycline Chemotherapy: A Sham-Controlled Single-Blind Randomized Trial

Yiu-Fai Cheung et al. JACC CardioOncol. .

Abstract

Background: Anthracycline cardiotoxicity is a concern in survivors of childhood cancers. Recent evidence suggests that remote ischemic conditioning (RIC) may offer myocardial protection.

Objectives: This randomized sham-controlled single-blind study tested the hypothesis that RIC may reduce myocardial injury in pediatric cancer patients receiving anthracycline chemotherapy.

Methods: We performed a phase 2 sham-controlled single-blind randomized controlled trial to determine the impact of RIC on myocardial injury in pediatric cancer patients receiving anthracycline-based chemotherapy. Patients were randomized to receive RIC (3 cycles of 5-minute inflation of a blood pressure cuff placed over 1 limb to 15 mm Hg above systolic pressure) or sham intervention. The intervention was applied within 60 minutes before initiation of the first dose and before up to 4 cycles of anthracycline therapy. The primary outcome was the plasma high-sensitivity cardiac troponin T (hs-cTnT) level. The secondary outcome measures included echocardiographic indexes of left ventricular systolic and diastolic function and the occurrence of cardiovascular events.

Results: A total of 68 children 10.9 ± 3.9 years of age were randomized to receive RIC (n = 34) or sham (n = 34) intervention. Plasma levels of hs-cTnT showed a progressive increase across time points in the RIC (P < 0.001) and sham (P < 0.001) groups. At each of the time points, there were no significant differences in hs-cTnT levels or LV tissue Doppler and strain parameters between the 2 groups (all P > 0.05). None of the patients developed heart failure or cardiac arrhythmias.

Conclusions: RIC did not exhibit cardioprotective effects in childhood cancer patients receiving anthracycline-based chemotherapy. (Remote Ischaemic Preconditioning in Childhood Cancer [RIPC]; NCT03166813).

Keywords: anthracycline; pediatric cancer; remote ischemic conditioning.

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Conflict of interest statement

This study was supported by the Health and Health Services Research Fund, Food and Health Bureau, Hong Kong SAR Government (grant 05161506). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Study Protocol Newly diagnosed pediatric cancer patients between 2018 and 2021 were screened for eligibility to be recruited into the study. hs-cTnT = high-sensitivity cardiac troponin T; RIC = remote ischemic conditioning.
Figure 2
Figure 2
Recruitment and Flow of Study Participants From January 2018 to December 2021, a total of 84 eligible patients were identified to be eligible for inclusion. Thirteen patients declined, and 3 withdrew before randomization; the remaining 68 were randomized to receive remote ischemic conditioning (RIC) or sham protocol.
Figure 3
Figure 3
Longitudinal Changes in Natural Log Transformed hs-cTnT Levels Natural log-transformed plasma levels of high-sensitivity cardiac troponin T (hs-cTnT) showed a progressive increase across the time points (TPs) in the remote ischemic conditioning group (denoted in red) and the sham group (denoted in blue). At each of the TPs, there were no significant differences between the 2 groups. The error bars represent least square mean ± 95% CI.
Figure 4
Figure 4
Longitudinal Changes in Natural Log-Transformed hs-cTnT Levels in Hematologic and Nonhematologic Malignancies The natural log-transformed plasma levels of hs-cTnT in (A) patients with hematologic malignancies and (B) patients with nonhematologic malignancies showed a progressive increase across the time points in both the remote ischemic conditioning group (denoted in red) and the sham group (denoted in blue). At each of the TPs, there were no significant differences in hs-cTnT between the 2 interventions in both patient groups. The error bars represent least square mean ± 95% CI. Abbreviations as in Figure 3.
Central Illustration
Central Illustration
Remote Ischemic Conditioning Did Not Result in Cardioprotective Effects in Childhood Cancer Patients Remote ischemic conditioning (RIC) did not have significant effects on the plasma levels of high-sensitivity cardiac troponin T (hs-cTnT), the parameters of left ventricular (LV) systolic and diastolic function, or the occurrence of cardiovascular events in childhood cancer patients undergoing anthracycline-based chemotherapy followed up until 3 months after completion of anthracycline therapy. BP = blood pressure.
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