Atrial fibrillation and heart failure with reduced ejection fraction - Investigation of additive mechanisms of pulmonary vein isolation

• Applicant: Dr. Andreas Böhmer
• Subject Area: Anatomy and Physiology ; Cardiology, Angiology
• Term: from 2024 to 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 551271872

The proposed research project is based on the hypothesis that the improvement of cardiac function and prognosis in atrial fibrillation and heart failure with reduced ejection fraction (primary endpoints of the CASTLE-AF and CASTLE-HTx studies) by means of pulmonary vein isolation - in addition to the permanent restoration of sinus rhythm - may be based on an iatrogenic atrial left-to-right shunt with hemodynamic relief of the left ventricle following transseptal puncture and, secondly, on a favorable modulation of the autonomic cardiac nervous system. To test this hypothesis, the heart failure dog model of the working group of Prof. Stanley Nattel (Montreal Heart Institute, Canada) will be used, in which heart failure is induced by 2-week ventricular tachypacing. After echocardiographic confirmation of heart failure, the following interventions will be performed: Group 1 (n=10): Transseptal puncture with pulmonary vein isolation. Group 2 (n=10): Transseptal puncture without pulmonary vein isolation Group 3 (n=10): Sham procedure without transseptal puncture or pulmonary vein isolation. 1 week after the above-mentioned interventions, invasive hemodynamic measurements (determination of shunt volume and ventricular filling pressures), echocardiography (LVEF, ventricular and atrial volumes), electrophysiological examination (atrial fibrillation inducibility) and histological examinations (quantification and characterization of autonomic properties and changes in fibroblastic mitochondria including production of reactive oxygen species) will be performed in all 3 groups. The project will be conducted under the direction of Prof. Dr. Stanley Nattel at the Montreal Heart Institute, Canada. All modalities for husbandry, instrumentation and examination of the animals have been established in the laboratory for decades, which ensures the effective execution of the research project.

• DFG Programme: WBP Fellowship
• International Connection: Canada
• Host: Professor Dr. Stanley Nattel