Dissertation Isotta Castrini
Cand.med. Anna Isotta Castrini from ProCardio defended the thesis “Pregnancy and progression of cardiac disease in genetic cardiomyopathies" for the degree of PhD (Philosophiae Doctor) on May 27, 2024. The trial lecture was titled “What is the utility of polygenic risk scores and genetic testing in cardiology in 2024?"
Published 5/31/2024
Last updated 8/8/2024
Public Defence: Anna Isotta Castrini - Institute of Clinical Medicine (uio.no)
Adjudication committee
First opponent: Professor Jacob Tfelt-Hansen, University of Copenhagen, Denmark
Second opponent: Professor Charlotte Bjørk Ingul, NTNU - Norwegian University of Science and Technology,
Third member and chair of the evaluation committee: Professor Torbjørn Omland, University of Oslo
Second opponent: Professor Charlotte Bjørk Ingul, NTNU - Norwegian University of Science and Technology,
Third member and chair of the evaluation committee: Professor Torbjørn Omland, University of Oslo
Chair of the Defence
Associate Professor John-Peder Escobar Kvitting, University of Oslo
Associate Professor John-Peder Escobar Kvitting, University of Oslo
Principal Supervisor
Professor II Kristina Ingrid Helena Hermann Haugaa, University of Oslo
Professor II Kristina Ingrid Helena Hermann Haugaa, University of Oslo
Summary
Genetic cardiomyopathies are hereditary cardiac diseases often diagnosed in young patients and are characterized by live-threatening arrhythmias and heart failure. Among them are arrhythmogenic (AC) and Lamin A/C cardiomyopathy. At genetic diagnosis, penetrance of the disease is often incomplete and factors promoting the disease progression are poorly recognized. Physical exercise is a hemodynamic stress and was previously associated with higher disease penetrance in AC and Lamin A/C cardiomyopathy. Pregnancy is also a hemodynamic stress, therefore with a potential detrimental effect on cardiac disease for patients with a genetic predisposition; however, the role of pregnancy as a factor potentially promoting disease progression in AC and Lamin A/C cardiomyopathy is poorly identified. The results of this thesis contributed to increase our knowledge in the field, showing no significant effect of pregnancy on long term structural and functional disease progression by echocardiography, and no major effect on arrhythmias, in AC and Lamin A/C cardiomyopathy. Additionally, we described the stages of disease progression in Lamin A/C cardiomyopathy, showing a high prevalence of electrical disease at young age, followed by left and right ventricular dysfunction, where the latter was independently associated with adverse prognosis.
Genetic cardiomyopathies are hereditary cardiac diseases often diagnosed in young patients and are characterized by live-threatening arrhythmias and heart failure. Among them are arrhythmogenic (AC) and Lamin A/C cardiomyopathy. At genetic diagnosis, penetrance of the disease is often incomplete and factors promoting the disease progression are poorly recognized. Physical exercise is a hemodynamic stress and was previously associated with higher disease penetrance in AC and Lamin A/C cardiomyopathy. Pregnancy is also a hemodynamic stress, therefore with a potential detrimental effect on cardiac disease for patients with a genetic predisposition; however, the role of pregnancy as a factor potentially promoting disease progression in AC and Lamin A/C cardiomyopathy is poorly identified. The results of this thesis contributed to increase our knowledge in the field, showing no significant effect of pregnancy on long term structural and functional disease progression by echocardiography, and no major effect on arrhythmias, in AC and Lamin A/C cardiomyopathy. Additionally, we described the stages of disease progression in Lamin A/C cardiomyopathy, showing a high prevalence of electrical disease at young age, followed by left and right ventricular dysfunction, where the latter was independently associated with adverse prognosis.