Biological Mechanisms Behind Resynchronization Therapy in Heart Failure

Heart failure is a common disease, affecting 2-3% of the population in the western world. About 30% of patients with heart failure and reduced ejection fraction display signs of electrical dyssynchrony on ECG, usually left bundle branch block (LBBB), which is associated with a worse prognosis. Cardiac resynchronization therapy (CRT) reduce mortality for patients with dyssynchronic heart failure, defined as ejection fraction (EF) = or \< 35% and LBBB. About 1/3 of the patients that fit CRT criteria will not respond to CRT. Which patients that will turn out to be non-responders cannot be anticipated beforehand.

We have started a clinical study to collect blood samples, heart tissue and clinical data 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.

Blood samples and tissue will be analysed in the search for (i) biomarkers to separate CRT responders from non-responders and (ii) mechanisms behind the remodelling observed in CRT and with medical therapy.

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.

Eligibility Criteria:
Inclusion Criteria:

1. Ejection fraction (EF) = or \< 35% and A or B

   A) Left bundle branch block (LBBB) QRS = or \> 150 ms or a high proportion ventricular pacing and planned for CRT at Karolinska University Hospital.

   B) Planned for medical treatment and followed at Karolinska University Hospital.
2. Ability to understand the given information.
3. Ability to give informed consent.

Exclusion Criteria:

1. Pregnant or planning pregnancy
2. Not able to give informed consent -