Biological Mechanisms Behind Resynchronization Therapy in Heart Failure

In dyssynchrony the conduction of electrical signals within the heart is prolonged causing a delay between the activation and contraction of septum and lateral left ventricular wall. In turn, this results in uncoordinated and ineffective heart work. Dyssynchrony is accompanied by cardiac remodeling with dilatation of the left chamber. Whether dilatation is an effect or a cause of dyssynchrony is unclear and likely different for different patients. Cardiac resynchronization therapy, CRT, is a pacemaker with an extra electrode that will stimulate the right and left ventricle simultaneously, resulting in resynchronization.

We have started a clinical study to collect blood samples, heart tissue and clinical data (echocardiography, ECG, medical records) from heart failure patients eligible for CRT and a control group of heart failure patients on medical therapy. Patients will be assessed before CRT implantation or early after initiation of medical treatment, at 3 months, 6 months and 12 months. A subset of the patients in the CRT group will also also be subjected to a heart biopsy before CRT implantation and at 3 months. At each time point all patients will be assessed with echocardiography, ECG and blood sampling. The blood samples will be analyzed regarding proteins and exosomal miRNA. The heart tissue will be frozen and analyzed regarding proteins, RNA and contractility.

Endothelial function is also known to play a crucial role in heart failure and will be evaluated at inclusion, 3 and 12 months using EndoPAT. Red blood cells (RBCs) are collected to determine whether they may affect endothelial cell function.