Can simulated ischemia training prior to chemotherapy reduce the damaging effects of anthracyclines (chemotherapy) on the heart?

Lymphomas are a group of diseases characterized by the formation of malignant blood cells; they are therefore a subtype of blood cancer. A commonly used treatment for lymphomas is chemotherapy with so-called anthracyclines. Anthracyclines are a group of chemotherapy drugs that kill cancer cells by damaging their genetic material (DNA) and thus blocking cell division. They are among the most effective drugs for many types of cancer, including lymphomas. A major problem, however, is their potential to damage the heart, as they can also cause damage to healthy heart muscle cells—especially with prolonged or high-dose use. The risk increases if pre-existing heart damage is present and as the patients’ age increases. Remote Ischemic Preconditioning (RIPC) is a medical procedure designed to specifically prepare the body for an impending stressor—such as surgery or a circulatory disturbance—in order to reduce tissue damage. In RIPC, blood flow to a limb (usually an arm or leg) is intentionally interrupted multiple times for short periods, for example, by inflating a blood pressure cuff. This causes a brief oxygen deprivation (ischemia), which serves as a “warning signal” to the body. This signal triggers protective mechanisms throughout the body—similar to the effects of exercise—and can help make organs such as the heart, brain, or kidneys more resilient to subsequent severe stress (e.g., heart attack, surgery, or stroke).

The goal of the RESILIENCE study is to investigate whether the use of RIPC could represent a novel method for protecting the heart during chemotherapy: Once a week throughout the entire course of chemotherapy, a blood pressure cuff on the arm is inflated and deflated four times for five minutes each. This controlled, brief interruption of blood flow is intended to make the heart more resilient to chemotherapy. The study is a randomized, blinded Phase 2 trial. This means that participants are randomly assigned to two groups. One group receives the actual RIPC treatment, while the other receives a sham treatment, in which the cuff is not inflated to sufficient pressure. Neither the participants nor the medical staff know who is receiving which treatment. To monitor heart function, cardiac and blood tests will be performed at various time points.

Eligible participants are adults aged 18 and older with a newly diagnosed lymphoma (e.g., Hodgkin’s or non-Hodgkin’s lymphoma) who are scheduled to receive at least five cycles of anthracycline therapy. A prerequisite is normal heart function before the start of treatment (left ventricular ejection fraction above 40%). In addition, participants must have at least one risk factor for potential heart damage, such as existing coronary heart disease, high blood pressure, impaired kidney function, diabetes, smoking, severe obesity (BMI ≥ 30), thickening of the heart muscle, heavy alcohol consumption, or being 65 years of age or older. Individuals are excluded from participation if they already have heart failure, persistent arrhythmias (e.g., atrial fibrillation), severe valvular heart disease, or peripheral vascular disease in the arms. Patients with implanted cardiac devices such as pacemakers or defibrillators, severe blood clotting disorders, or those who have previously received anthracyclines are also ineligible to participate.