Effect of Remote Ischemic Conditioning in Patients With Chronic Ischemic Heart Failure (CONDI-HF)

Background Chronic heart failure (CHF) is a leading cause of morbidity and mortality throughout the world, and the incidence and prevalence are increasing as more patients survive their acute coronary syndrome. The disease is caused by abnormalities in cardiac structure or function leading to insufficient delivery of oxygen to the metabolizing tissues. These patients are often debilitated, require chronic medications, and many receive expensive device therapy to manage symptoms. Consequently, this has led to an increasing economic and health burden from heart failure.

CHF is the end-stage of a broad range of underlying cardiovascular diseases, but is most frequently caused by ischemic heart disease. Other contributory causes include hypertension, heart valve diseases, arrhythmias and cardiomyopathies, all resulting in myocardial tissue damage and loss of ventricular function. Activation of neurohormonal and inflammatory compensatory mechanisms lead to a vicious circle through adaptive metabolic and remodeling processes, eventually resulting in a progressive decline of cardiac function with significant morbidity and mortality.

Identification of the specific underlying cardiac condition is crucial for the therapeutic approach in patients suffering from CHF. While pharmacological treatment remains dominating, resynchronization therapy and surgical resection of non-contractile tissue are also increasingly being conducted. Despite the fact that activation of the inflammatory system greatly contributes to the remodeling process through initiation of myocardial fibrosis and hypertrophy, most clinical studies targeting inflammatory components have been discouraging.

Remote ischemic conditioning (RIC) by brief non-lethal episodes of ischemia in a remote organ or tissue (e.g. a limb) is a novel therapeutic method to achieve protection against ischemia-reperfusion injury in the target organ, e.g. the heart . In the clinical setting, RIC is most often performed by repeated episodes of limb ischemia achieved by intermittent inflation of a blood pressure cuff placed around the upper arm. In clinical randomized trials, RIC has been shown to reduce the amount of myocardial injury and improve long-term outcome in patients admitted with STEMI for primary percutaneous coronary intervention and patients undergoing cardiac surgery or elective coronary intervention.

RIC is a low-cost, simple and safe procedure that can easily be conducted using a standard blood pressure cuff, and the method is increasingly used in clinical trials. The mechanisms behind RIC are not yet fully understood, but the cardioprotective effects are believed to be caused by neural and humoral signaling cascades as well as systemic anti-inflammatory effects resulting in a cytoprotective state. In addition, RIC has been shown to reduce thrombus formation. Since activation of platelets and the coagulation system are fundamental in thrombus formation and degradation, another possible mechanism of the described effects of RIC could be a result from effect on arterial thrombus formation.