Clinical phenotypes in heart failure defined by cardiac magnetic resonance feature tracking and parametric mapping

Thesis

In this thesis I applied cardiovascular magnetic resonance (CMR) feature tracking (FT) and parametric mapping, along with more general CMR and echocardiography methods and other specific methods (e.g. biochemistry, endomyocardial biopsy) to characterize various types of cardiac remodelling associated with heart failure (HF) or conditions that create cardiac dysfunction potentially associated to a preclinical phenotype of HF (patients with elevated left ventricular filling pressures, treated phenylketonuria and convalescent patients recovered from COVID-19).

My results indicate the important and specific role of FT CMR in quantification of functional deficit associated with HF. A multilayer systolic peak strain comparison individuates subendocardium as a particularly sensitive region of the myocardium for quantification of myocardial strain. I showed that Endo-Epi circumferential strain gradients, in particular, are progressively blunted in HFmrEF (Heart Failure with midrange Ejection Fraction) and HFrEF (Heart Failure with reduced Ejection Fraction) but remain at physiological levels in HFpEF (Heart Failure with preserved Ejection Fraction). I further showed the feasibility and importance of this technique in assessing phasic emptying fractions and strains of the left atrium and proposed CMR criteria for the diagnosis of a newly described clinical entity, atrial failure. Following this line, I characterized what elements of LV remodelling related to atrial failure or phasic dysfunction. I further applied FT and derived mathematical models for systolic and diastolic hemodynamic forces approximation to characterize CMR surrogates of catheter-measured LV end-diastolic pressure. Here, I characterized for the first time the cardiac phenotype of adult patients with phenylketonuria, who demonstrate reduced myocardial mass and structural modifications related to their persistent metabolic abnormalities and showed the importance of life-long phenylalanine control in preventing adverse cardiac remodelling. I compared the cardiac manifestations of COVID-19 with the ones observed in non-SARS-CoV2 viral myocarditis and point to a slower functional recovery in patients with more severe disease presentation and intense hospital care.

Authors: Tanacli, R

• DOI: 10.5287/ora-yqg0qxp8j
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: heart failure; cardiomyopathy; cardiac remodeling; cardiac magnetic resonance; parametric mapping; feature tracking; phenylketonuria
• Subjects: Cardiology, Heart Failure, Myocardial Biology, Imaging, Metabolic Disease